Showing papers by "Loma Linda University published in 1991"

Bone growth factors.

Abstract: Bone volume is determined by the relative rates of bone formation and bone resorption. Recent research in several laboratories suggests that growth factors may act locally to modulate bone formation by stimulating osteoblast proliferation and activity. A number of bone-derived growth factors have been isolated and characterized from bone matrix extracts and from media conditioned by bone cells and bone organs in culture. The growth factors found in bone matrix include insulinlike growth factors I and II, transforming growth factor-beta, acidic and basic fibroblast growth factor, platelet-derived growth factor, and bone morphogenetic proteins. Conditioned medium from bone cells contains several of these growth factors and also hematopoietic factors. These bone matrix-derived growth factors have different biologic activities, including mitogenic, differentiating, chemotactic, and osteolytic activities. Evidence suggests that bone cells produce substantial quantities of growth factors for extracellular storage in bone matrix. Apart from being produced for extracellular storage, it is possible that growth factors secreted by bone cells have acute effects on their neighboring osteoblastic cells, i.e., paracrine action, or on themselves, i.e., autocrine action. The release of matrix-stored growth factors by bone resorption may mean that growth factors act as delayed paracrine agents, e.g., osteoblasts deposit growth factors in bone and later when these growth factors are released from bone via bone resorption, the growth factors stimulate osteoblast precursors to proliferate. The findings that bone is a storehouse for growth factors and that bone cells in culture produce and respond to bone growth factors suggest bone growth factors may act as potential determinants of local bone formation. This review is focused on the structure, regulation, and biologic actions of the known bone growth factors.

An evaluation of the susceptibility patterns of Gram-negative organisms isolated in cancer centres with aminoglycoside usage

Abstract: This study in 12 cancer treatment centres across the United States was designed to evaluate the potential for increased resistance to amikacin with unrestricted use. An initial 3-month baseline period during which the use of amikacin was restricted and that of tobramycin and gentamicin unrestricted was followed by a period of at least 12 months when amikacin was the primary aminoglycoside. Resistance of Gram-negative bacilli to these aminoglycosides from hospitalized patients was monitored and compared for the two periods. Amikacin usage increased from a mean of 20.1% to a mean of 83.9% of aminoglycoside patient-days. A reduction in the use of tobramycin and gentamicin were observed with means of 66.1 and 10%, and 13.9 and 6.1%, respectively for the two periods. Resistance to amikacin was 0.85% at baseline and 1.3% at end-point which was not clinically significant (P = 0.614). Baseline resistance was 6.5 and 7.6%, while final resistance was 2.6 and 4.8%, respectively for tobramycin (P = 0.001) and gentamicin (P = 0.052).

Body mass index and patterns of mortality among Seventh-day Adventist men.

Abstract: This study examines the relationship between body mass index (BMI) and 26-year mortality among 8828 nonsmoking, nondrinking Seventh-day Adventist men, including 439 who were very lean (BMI less than 20 kg/m2). The adjusted relative risk comparing the lowest BMI quintile (less than 22.3) to the highest (greater than 27.5 kg/m2) was 0.70 (95 percent CI 0.63-0.78) for all cause mortality, 0.60 (95 percent CI 0.43-0.85) for cerebrovascular mortality, and 0.80 (95 percent CI 0.61-1.04) for cancer mortality. Very lean men did not show increased mortality. To assess whether the protective effect associated with low BMI is modified by increasing age, the product term between BMI and attained age (age at the end of follow-up or at death) was included as a time-dependent covariate. For ischemic heart disease mortality, age-specific estimates of the relative risk for the lowest quintile relative to the highest ranged from 0.32 (95 percent CI, 0.19-0.52) at age 50 to 0.71 (95 percent CI, 0.56-0.89) at age 90. Interaction was also seen for the next lowest quintile (22.4-24.2). There was a significant trend of increasing mortality with increasing BMI for all endpoints studied. For cancer and cerebrovascular mortality the P-values for trend were 0.0001 and 0.001 respectively. For the other endpoints the P-values were less than 0.0001. Thus, there was no evidence for a J-shaped relationship between BMI and mortality in males. While the protective effect associated with the lowest BMI quintile decreased with increasing age for ischemic heart disease mortality, it remained greater than one at all ages. The relatively large number of subjects who were lean by choice, rather than as a result of preclinical disease or smoking, may explain these findings.

A comparison of the cerebral protective effects of isoflurane and mild hypothermia in a model of incomplete forebrain ischemia in the rat.

Abstract: The present study was undertaken to examine the cerebral protective properties attributed to isoflurane and at the same time to compare its protective effects with those of mild hypothermia (temperature reduction by 3° C). Twenty-one fasted Wistar-Kyoto rats were assigned to one of three groups (n = 7): 1.3 MAC (end-tidal) isoflurane-normothermia (pericranial temperature 38.0° C), 1.3 MAC halothane-normothermia, and 1.3 MAC halothane-hypothermia (pericranial temperature 35.0° C during ischemia). In each animal the trachea was intubated and the lungs were mechanically ventilated. Each animal was subjected to temporary incomplete forebrain ischemia induced by 10 min of bilateral carotid artery occlusion with simultaneous hypotension (mean arterial pressure 35 mmHg) induced by trimetaphan and blood withdrawal. After a 3-day survival period, perfusion-fixation was performed, and two blinded observers assessed histopathologic injury according to a four-point scale (0 = no damage; 1 = 50% damaged). The assessment was performed at two points in the rostrocaudal axis chosen to permit evaluation of regions with varying levels of ischemic damage. In the rostral sections, in the isoflurane- and halothane-normothermia groups, moderate to severe injury was observed in striatum, cerebral cortex, hippocampus (CA1 and CA3 areas), and reticular nucleus of the thalamus (e.g., the median scores for the CA1 area were 3 in both the halothane-normothermia and the isoflurane-normothermia groups), and there were no differences between the two groups. By contrast, the halothane-hypothermia group showed significantly less damage (e.g., the median score for the CA1 area was 1) in all but the hippocampal CA3 area. In the caudal section, the injury was significantly less severe in portions of the cortex and hippocampal CA1. As in the rostral sections, the degree of damage did not differ between the two normothermia groups, but was significantly less severe in the halothane-hypothermia group. The data indicate that in the circumstances of the present study, isoflurane did not confer protection relative to control animals anesthetized with an eouipotent concentration of halothane, but that mild intraischemic hypothermia (by 3° C) was markedly protective.

Persistent sacral nerve root deficits after continuous spinal anaesthesia.

Abstract: Neurological deficits following spinal anaesthesia are rare. We report two cases of persistent sacral nerve root deficits after continuous spinal anaesthesia (CSA) performed with hyperbaric lidocaine through a lumbar microcatheter. In both cases the dose of 5% lidocaine (5.7 and 4.3 ml) was greater than usual. In the immediate postoperative period the constellation of neurological deficits included perianal hypaesthesia, lower extremity paresis, urinary retention, and difficult defaecation. Both patients have residual perianal hypaesthesia and difficult defaecation. In these cases, the high-dose requirements of local anaesthetic via microcatheter CSA with focal sensory block suggests nonuniform distribution of the hyperbaric lidocaine. Microcatheter CSA may convey a unique risk of maldistribution of the local anaesthetic solution and local neurotoxicity.

Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms' Tumor Study Pathology Center.

Abstract: Fifty-six renal neoplasms reviewed by the National Wilms' Tumor Study Pathology Center presented with histologic features that resulted in confusion with rhabdoid tumor of kidney, a usually lethal childhood renal tumor; all were eventually diagnosed as other entities. Conspicuous filamentous cytoplasmic inclusions or large nucleoli, typical findings in rhabdoid renal tumors, were the usual source of diagnostic difficulty. Most, but not all, tumors occurred in pediatric patients. Sixteen were examples of Favorable Histology Wilms' tumor, which invited confusion with rhabdoid tumors either on the basis of filamentous cytoplasmic inclusions (15 cases) or macronucleoli (one case). In most cases, foci of typical Wilms' tumor blastemal aggregation or evidence of definitive nephrogenic differentiation facilitated the correct diagnosis. All 10 patients for whom information about outcome was available were alive at last follow-up. The other 40 renal lesions mimicking rhabdoid tumor of kidney consisted of a clinically and histogenetically diverse group of neoplasms, including anaplastic Wilms' tumor, congenital mesoblastic nephroma, renal cell carcinoma, transitional cell carcinoma, collecting-duct carcinoma, oncocytoma, rhabdomyosarcoma, malignant neuroepithelial tumors, and lymphoma. Most of these lesions could be separated from renal rhabdoid tumors and correctly classified on the basis of careful attention to light microscopic details, but in several cases electron microscopy or immunocytochemical studies were helpful or essential.

Vitamin D deficiency causes a selective reduction in deposition of transforming growth factor beta in rat bone: possible mechanism for impaired osteoinduction.

Abstract: We demonstrated previously that implants of bone matrix prepared from vitamin D-deficient (-D) rats were less osteoinductive and contained less extractable mitogenic activity compared with control implants prepared from vitamin D-replete (+D) rats and proposed that bone from -D rats is deficient in one or more specific growth factors. To test this hypothesis, bones from rats that were fed either +D or -D diets and kept in the dark for 8 wk were extracted and assayed for insulin-like growth factors I and II (IGF-I and IGF-II) and transforming growth factor beta (TGF-beta), the three most abundant growth factors in rat bone, and osteocalcin. Serum calcium, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were determined at sacrifice. In -D rats, there were significant reductions in serum calcium, 25-hydroxyvitamin D3, and 1,25(OH)2D3 and skeletal TGF-beta but no differences in extractable skeletal protein, IGF-I, IGF-II, or osteocalcin compared with +D rats. To determine whether 1,25(OH)2D3 increased TGF-beta production by bone cells, we treated mouse calvaria for 6 days and mouse osteoblasts for 2 days with 10 nM 1,25(OH)2D3. Production of TGF-beta was increased almost 100% by 1,25(OH)2D3. We conclude that vitamin D deficiency reduces deposition of TGF-beta in rat bone and that diminished skeletal TGF-beta could contribute to the previously observed decrease in osteoinduction in implants from -D rat bone. The findings support the possibility that vitamin D and bone-derived TGF-beta are required for normal repair of the skeleton.

Garlic compounds modulate macrophage and T-lymphocyte functions.

Abstract: Organosulfur compounds of garlic have been shown to inhibit growth of animal tumors and to modulate the activity of diverse chemical carcinogens. There is also evidence that garlic may modulate antitumor immunity. In this study, we determined the effects of an aqueous garlic extract and a protein fraction isolated from the extract on the chemiluminescent oxidative burst of the murine J774 macrophage cell line and thioglycollate-elicited peritoneal macrophages obtained from BALB/c mice. T-lymphocyte activity was determined using mouse splenocytes incubated with phytohemagglutinin, labeled with [3H]-thymidine and assayed for lymphoproliferation. Significant dose-related augmentation of oxidative burst was observed with garlic extract and the protein fraction. The protein fraction also enhanced the T-lymphocyte blastogenesis. The data suggest that garlic compounds may serve as biological response modifiers by augmenting macrophage and T-lymphocyte functions.

Using theoretical descriptors in quantitative structure-activity relationships: some toxicological indices

Abstract: The application of computational techniques to medicinal chemistry is growing at a tremendous rate. Quantitative structure-activity relationships (QSAR), which relate biological and toxicological activities to structural features, have been employed widely to correlate structure to activity. A difficulty of this approach has been nonuniformity of parameter sets and the inability to examine contributions across properties and data sets. Linear solvation energy relationships (LSER) developed by Kamlet and Taft circumvent many of the difficulties and successfully utilize a single set of parameters for a wide range of physical, chemical, and biological properties. We have replaced the LSER solvato-chromatic parameters with theoretically determined parameters to permit better a priori prediction of properties. Comparison of the two parameter sets for five biological activities is presented, showing the excellent fit of the theoretically determined parameters.

Multidimensionality and state dependency of alexithymia in recently sober alcoholics.

Abstract: In this study, we a) examined the appropriateness of using a single global score to represent alexithymia and b) constructed a model to examine the relationship between alexithymia and depression in recently sober alcoholics applying for inpatient care. To measure alexithymia, we used the Toronto Alexithymia Scale (TAS); to measure depression, we used the revised Beck Depression Inventory (BDI). Factor analyses identified three alexithymia factors (Feelings, Daydreaming, and External Thinking) and two depression factors (Somatic-Performance and Cognitive-Affective). The three TAS factors were not positively related to each other; the two BDI factors were. We used LISREL software to examine the relationships between the TAS factors and the BDI factors. The only two significant unidirectional coefficients were between the TAS-Feelings factor and the two BDI factors. Our results suggest that in recently sober alcoholics, alexithymia, as measured by the TAS, consists of three independent, unrelated dimensions. Moreover, only the dimension associated with an inability to identify feelings and to distinguish them from bodily sensations is related to depressive symptoms. To determine whether this alexithymia feelings dimension actually is dependent on situational depression and/or anxiety will require confirmation in additional samples, such as primary alexithymics and patients with major depressive disorders.

A comparison of proximal plaque removal using floss and interdental brushes

Abstract: The removal of interproximal plaque was compared using a standard toothbrush alone, a toothbrush with unwaxed dental floss and a toothbrush with an interdental brush. 30 previously treated periodontal patients were given the cleaning aids in a three-way crossover study design. After each 1 month trial period, scores for gingivitis, buccal/lingual plaque and proximal plaque were recorded. Mean GI scores for subjects were 0.37 using the toothbrush only, 0.36 using the toothbrush with floss and 0.32 using the toothbrush with the interdental brush. Mean buccal/lingual plaque scores were 0.64 using the toothbrush only, 0.62 using the toothbrush with floss and 0.51 using the toothbrush with the interdental brush. Mean plaque scores were 2.32 with the toothbrush only, 1.71 using the toothbrush with floss and 1.22 using the toothbrush with the interdental brush. Statistically significant differences were seen in proximal plaque scores between the 3 treatment groups. The results indicate that the interdental brush used in combination with a toothbrush is more effective in the removal of plaque from proximal tooth surfaces than a toothbrush used alone or in combination with dental floss.

The effects of acute moderate exercise on leukocyte and lymphocyte subpopulations.

Abstract: The extent and duration of changes in circulating leukocyte and lymphocyte subpopulations, cortisol, and catecholamines were examined in 12 women who walked 45 min at 60% VO2max in a laboratory setting. A two-factor, 2 x 6 design with repeated measures on both factors was utilized. The first factor was condition (exercise and rest), and the second factor was time (six points of measurement over a 24-h period), with treatment order counterbalanced. The 45-min walk, in comparison with rest in a seated position, was associated with a significant but moderate leukocytosis and lymphocytosis immediately following the walk. The leukocytosis was still evident after 3 h of recovery and was primarily due to a neutrophilia. The change in lymphocyte count, relative to baseline levels and the control condition, lasted less than 1.5 h, with an increase in the natural killer (CD16 and/or CD56) and cytotoxic T cell component (CD3 and CD16 and/or CD56) (NKCT) representing approximately two-thirds of the lymphocytosis and T cells (CD5) the other third. A significant decrease in the CD4:CD8 ratio was seen, with cytotoxic/suppressor (CD8) cells increasing and helper/inducer (CD4) cells demonstrating little change in comparison with baseline. This seems to have been due to a subpopulation of CD8 (low density antigen) cells, probably natural killer cells. The 45-min walk had no effect on plasma cortisol and epinephrine levels relative to the rest condition but was associated with a moderate increase in norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term ambient concentrations of total suspended particulates and oxidants as related to incidence of chronic disease in California Seventh-Day Adventists.

Abstract: Cancer incidence and mortality in a cohort of 6000 nonsmoking California Seventh-Day Adventists were monitored for a 6-year period, and relationships with long-term cumulative ambient air pollution were observed. Total suspended particulates (TSP) and ozone were measured in terms of numbers of hours in excess of several threshold levels corresponding to national standards as well as mean concentration. For all malignant neoplasms among females, risk increased with increasing exceedance frequencies of all thresholds of TSP except the lowest one, and those increased risks were highly statistically significant. For respiratory cancers, increased risk was associated with only one threshold of ozone, and this result was of borderline significance. Respiratory disease symptoms were assessed in 1977 and again in 1987 using the National Heart, Lung and Blood Institute respiratory symptoms questionnaire on a subcohort of 3914 individuals. Multivariate analyses which adjusted for past and passive smoking and occupational exposures indicated statistically significantly (p less than 0.05) elevated relative risks ranging up to 1.7 for incidence of asthma, definite symptoms of airway obstructive disease, and chronic bronchitis with TSP in excess of all thresholds except the lowest one but not for any thresholds of ozone. A trend association (p = 0.056) was noted between the threshold of 10 pphm ozone and incidence of asthma. These results are presented within the context of standards setting for these constituents of air pollution.

Developmental changes in ovine cerebral artery composition and reactivity.

Abstract: We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.

The effects of acute moderate exercise on lymphocyte function and serum immunoglobulin levels.

Abstract: The extent and duration of changes on lymphocyte function and serum immunoglobulin (Ig) levels were examined in 12 women who walked 45 min at 60% VO2 max in a laboratory setting. A 2-factor, 2 x 6 design with repeated measures on both factors was utilized. The first factor was condition (exercise and rest), and the second factor was time (six times of measurement over a 24-h period), with treatment order counterbalanced. The 45-min walk, in comparison to rest in a seated position, was not associated with significant changes in circulating numbers of interleukin-2-activated T cells (CD5 and CD25) or on spontaneous or concanavalin-A-stimulated lymphocyte proliferation. A trend for decreased phytohemagglutinin-stimulated lymphocyte proliferation in comparison to the rest condition, however, was seen 1.5 h following the exercise bout (p = 0.047). The patterns of change for serum IgG, IgA, and IgM were significantly different (p = 0.001, p less than 0.001, p = 0.010, respectively) between conditions. IgG rose 7.2% immediately following exercise, and then returned to baseline 1.5 h later, which contrasted significantly with changes in the rest condition. These same patterns of change occurred also with IgA and IgM, but increases immediately following exercise were not significant, although a trend was seen for IgA (p = 0.03). The 45-min walk had no effect on plasma cortisol and epinephrine levels relative to the rest condition, but was associated with a significant 89% increase in norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Periodontal repair in dogs. Effect of heparin treatment of the root surface.

Abstract: Studies on periodontal repair to denuded root surfaces have suggested that initial clot adhesion to the root surface may be important for the nature of subsequent healing. To study this hypothesis, circumferential periodontal defects, approximately 5 mm in vertical dimensions, were surgically created and immediately treated around the mandibular premolars in 4 beagle dogs. Prior to wound closure, the root surfaces were treated with either the anticoagulant heparin or with saline. Tissue blocks were obtained at sacrifice 4 weeks after surgery. Histometric analysis showed that connective tissue repair to the root surface averaged 50% of the defect height for heparin-treated teeth as compared to 95% for saline-treated teeth. Junctional epithelium amounted to an average of 33% of the defect height in heparin-treated teeth in contrast to 5% following saline treatment. It can be concluded that heparin treatment of the root surface compromises connective tissue repair, confirming clot adhesion as one prerequisite for connective tissue repair of periodontal defects.

Periodontal repair in dogs Healing patterns in large circumferential periodontal defects

Abstract: This report describes the healing patterns of large circumferential periodontal defects in the beagle dog. Approximately 5 mm large periodontal defects were created around the mandibular premolars (P2, P3 and P4) in 13 animals. The root surfaces were then instrumented to remove all cementum and the wounds immediately closed by replacing and suturing the flaps just coronal to the cemento-enamel junction. Block biopsies were harvested after 4 weeks. Most of the surgically denuded root surface healed with connective tissue repair. Cementum formation and regeneration of alveolar bone was limited and averaged approximately 30% and 20%, respectively, of the defect height. Almost all teeth exhibited root resorption. Ankylosis was observed in 1/3 of the teeth. There was no difference in the healing response between the 3 premolars or their buccal and lingual surfaces. The range of healing responses indicates that a biological potential exists which makes this model useful for testing the effect of various root and wound conditioners in (1) enhancing cementum formation on the root surface, (2) increasing regeneration of alveolar bone and (3) preventing aberrant healing events such as root resorption and ankylosis. Conversely, whether such agents may compromise wound healing and result in reduced connective tissue repair may concomitantly be tested.

The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study.

Abstract: Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage.

Early healing events at the dentin-connective tissue interface. Light and transmission electron microscopy observations.

Abstract: The objective of these studies was to follow early healing at the dentin-connective tissue interface. Small dentin blocks were surgically implanted in bone cavities under mucoperiosteal flaps in the edentulous alveolar ridges of five beagle dogs at various times. In two separate experiments, wound maturation on native dentin surfaces and on citric acid or heparin conditioned dentin surfaces was observed. Block specimens including bone, dentin, and surrounding soft tissues were obtained at 10 minutes, 1 and 6 hours, and 1, 3, and 7 days after flap closure and prepared for light and transmission electron microscopic examination of the interface. The very initial attachment to native dentin was mediated by a granular precipitate. At 1 and 6 hours, the intercellular matrix was more organized with fibrin formation around red blood cell aggregates and at the dentin surface. Polymorphonuclear leukocytes were observed throughout the interface. Red blood cells were undergoing degradation at day 1 and polymorphonuclear cells were prevalent at the dentin surface. The 3-day observation interval was characterized by further maturation of the fibrin clot. Macrophages were observed near the dentin surface and fibroblasts could be identified. The 7-day specimens exhibited areas of cell rich connective tissue attachment without inflammatory cells as well as areas showing the fibrin clot in various stages of decomposition. These observations suggest that connective tissue attachment to dentin surfaces is mediated by adsorption of plasma proteins to the surface and subsequent development and maturation of a fibrin clot. The sequence of healing events at dentin surfaces conditioned with citric acid or heparin was largely similar to healing at native dentin surfaces. However, at day 1 and later time points, clot adhesion to heparin-conditioned dentin appeared compromised, whereas the fibrin clot seemed to adhere to citric acid-conditioned dentin at all observation periods. These observations indicate that in the absence of mechanical trauma, epithelial proliferation, and infection, wound maturation at the dentin-connective tissue interface may not necessarily be affected by treatments that either enhance or inhibit clot adhesion to the dentin surface.

Aluminum stimulates the proliferation and differentiation of osteoblasts in vitro by a mechanism that is different from fluoride.

Abstract: Micromolar concentrations of aluminum sulfate consistently stimulated [3H]thymidine incorporation into DNA and increased cellular alkaline phosphatase activity (an osteoblastic differentiation marker) in osteoblast-line cells of chicken and human. The stimulations were highly reproducible, and were biphasic and dose-dependent with the maximal stimulatory dose varied from experiment to experiment. The mitogenic doses of aluminum ion also stimulated collagen synthesis in cultured human osteosarcoma TE-85 cells, suggesting that aluminum ion might stimulate bone formation in vitro. The effects of mitogenic doses of aluminum ion on basal osteocalcin secretion by normal human osteoblasts could not be determined since there was little, if any, basal secretion of osteocalcin by these cells. 1,25 Dihydroxyvitamin D3 significantly stimulated the secretion of osteocalcin and the specific activity of cellular alkaline phosphatase in the human osteoblasts. Although mitogenic concentrations of aluminum ion potentiated the 1,25 dihydroxyvitamin D3-dependent stimulation of osteocalcin secretion, they significantly inhibited the hormone-mediated activation of cellular alkaline phosphatase activity. Mitogenic concentrations of aluminum ion did not stimulate cAMP production in human osteosarcoma TE85 cells, indicating that the mechanism of aluminum ion does not involve cAMP. The mitogenic activity of aluminum ion is different from that of fluoride because (a) unlike fluoride, its mitogenic activity was unaffected by culture medium changes; (b) unlike fluoride, its mitogenic activity was nonspecific for bone cells; and (c) aluminum ion interacted with fluoride on the stimulation of the proliferation of osteoblastic-line cells, and did not share the same rate-limiting step(s) as that of fluoride. PTH interacted with and potentiated the bone cell mitogenic activity of aluminum ion, and thereby is consistent with the possibility that the in vivo osteogenic actions of aluminum ion might depend on PTH. In summary, low concentrations of aluminum ion could act directly on osteoblasts to stimulate their proliferation and differentiation by a mechanism that is different from fluoride.

Dose-dependent effects of tamoxifen on long bones in growing rats: influence of ovarian status.

Abstract: Tamoxifen is a nonsteroidal antiestrogen which has been reported by various investigators to have estrogen agonist and antagonist effects on rat bone. These different interpretations may be due to differences in the ovarian status, estrogen levels, and/or tamoxifen levels of the rats. To address this issue, a dose response was determined for the effects of tamoxifen on bone histomorphometry in intact female and ovariectomized (OVX) rats. The results were compared with those obtained after treatment of OVX rats with estrogen alone or a combination of estrogen and tamoxifen. OVX resulted in increases in growth rate (weight gain) and periosteal bone formation rate and decreases in uterine weight and cancellous bone fractional volume (BV/TV). Treatment of OVX rats with estrogen resulted in dose-dependent decreases in growth rate and periosteal bone formation rate as well as dose-dependent increases in uterine weight and BV/TV. Similarly, tamoxifen treatment resulted in dose-dependent decreases in overall grow...

Skeletal alkaline phosphatase specific activity is an index of the osteoblastic phenotype in subpopulations of the human osteosarcoma cell line SaOS-2

Abstract: During continuous culture with serial passage, the human osteosarcoma cell line SaOS-2 showed a time-dependent decrease in skeletal alkaline phosphatase (ALP) activity. Because this was indicative of heterogeneity, subpopulations of SaOS-2 cells were isolated from replicate low-density cultures. The subpopulations were less heterogeneous and more stable (with respect to ALP) than the parent population. ALP specific activity in the subpopulations ranged from 0.05 to 2.3 U/mg protein, and cytochemical analyses indicated multiple steady-state levels of ALP activity per cell. The amount of ALP activity in SaOS-2 subpopulations was proportional to collagen production ([3H]proline incorporation into collagenase-digestible protein; r = .84, P less than .005), and to parathyroid hormone (PTH)-linked synthesis of cyclic adenosine monophosphate (cAMP) (r = .88, P less than .01). From these data, we inferred that ALP activity in SaOS-2 cells can provide a useful index of the osteoblastic phenotype, and that ALP activity, collagen production, and PTH-linked adenylate cyclase were coordinately regulated in these osteoblast-like osteosarcoma cells (ie, selection of subpopulations for ALP activity coselected for collagen synthesis and PTH-linked synthesis of cAMP). Further comparative studies showed that micromolar fluoride concentrations stimulated cell proliferation ([3H]thymidine incorporation into DNA) in low-ALP SaOS-2 subpopulations, but not in high-ALP cells (P less than .001), and that this differential sensitivity to fluoride was associated with an inverse correlation between fluoride-sensitive acid phosphatase and ALP activities (r = -.91, P less than .001).