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Biomedical subjects

I Bab

Publications and source records attributed to I Bab.

At least 19 recordsLinked to original sources
PubMed1992

Histone H4-related osteogenic growth peptide (OGP): a novel circulating stimulator of osteoblastic activity.

It has been established that regenerating marrow induces an osteogenic response in distant skeletal sites and that this activity is mediated by factors released into the circulation by the healing tissue. In the present study we have characterized one of these factors, a 14 amino acid peptide named osteogenic growth peptide (OGP). Synthetic OGP, identical in structure to the native molecule, stimulates the proliferation and alkaline phosphatase activity of osteoblastic cells in vitro and increases bone mass in rats when injected in vivo. Immunoreactive OGP in high abundance is present physiologically in the serum, mainly in the form of an OGP-OGP binding protein complex. A marked increase in serum bound and unbound OGP accompanies the osteogenic phase of post-ablation marrow regeneration and associated systemic osteogenic response. Authentic OGP is identical to the C-terminus of histone H4 and shares a five residue motif with a T-cell receptor beta-chain V-region and the Bacillus subtilis outB locus. Since these latter proteins have not been implicated previously in the control of cell proliferation or differentiation, OGP may belong to a novel, heretofore unrecognized family of regulatory peptides. Perhaps more importantly, OGP appears to represent a new class of molecules involved in the systemic control of osteoblast proliferation and differentiation.

Amino Acid Sequence↗
PubMed1992

Tissue response following CO2 laser application in apical surgery: light microscopic assessment in dogs.

The potential advantages of CO2 laser in apical surgery have not been established histologically. Therefore, the long-term effects of CO2 laser on the apical and periapical tissues were examined histologically in dogs 6 months after apical surgery. Lased specimens and unlased controls showed periapical inflammatory and osteogenic reactions. Lased root surfaces revealed craters with a superficial charred layer closely associated with new cementum-like matrix. The subjacent dentin appeared tubule-free and eosinophilic. Lased bone trabeculae showed a charred layer with a deeper osteocyte-free zone. The charred layer was covered by new bone. Detached charred segments in the marrow space and periapical inflammatory infiltrate were intimately associated with multinucleated giant cells, some containing minute char particles. Such cells were absent from the root and trabecular char linings. In addition, the charred surfaces were free of hard tissue resorption. These results suggest that CO2 laser does not hinder healing when applied in apical surgery.

Alveolar Process↗
PubMed1992

A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition.

Adolescent↗
PubMed1991

Histological characterization of bleaching-induced external root resorption in dogs.

External root resorption occasionally develops after intracoronal bleaching with hydrogen peroxide. In this study, an experimental model was established to study thermocatalytic bleaching-induced root resorption in dogs. Histological examination after 6 months revealed that 18% of the teeth had root resorption lesions. The lesions could be divided into three types. In type I, root excavations were associated with a dense inflammatory cell infiltrate. Type II lesions were characterized by granulation tissue formation. In type III, the lesions were filled with reparative cementum. The three types probably represent different phases of one process. Calcium hydroxide had no effect on the occurrence or type of resorption. The instability of hydrogen peroxide and the presence of inflammatory resorption lesions 6 months postoperatively suggest hydrogen peroxide-induced toxic radicals or denaturants as potential irritants.

Animals↗
PubMed1990

Osteochondral differentiation and the emergence of stage-specific osteogenic cell-surface molecules by bone marrow cells in diffusion chambers.

The osteochondral potential and emergence of osteogenic cell-surface molecules by avian marrow cells was evaluated in in vivo diffusion chamber cultures. The chambers were inoculated with unselected marrow cells from young chick tibiae and implanted intraperitoneally into athymic mice. At the light microscopic level, morphologic evidence of de novo bone and cartilage formation, including specific immunostaining by antibody probes, was observed in 14 out of 16 chambers incubated for 20 days or longer. In order to monitor the osteogenic differentiation of the marrow-derived cells, indirect immunofluorescence was performed with monoclonal antibodies against stage-specific cell surface antigens on cells of the embryonic osteogenic lineage. The binding of these and other specific monoclonal antibodies in the developing tissue indicates that the cell surface and extracellular matrix molecules expressed by descendants of marrow-derived mesenchymal progenitor cells are indistinguishable from their in vivo counterparts found in embryonic skeletal structures. Furthermore, the experiments reported here describe the first molecular identification of osteogenic cells by probes which are selective for stage-specific surface antigens on cells of the osteogenic lineage. Importantly, bone formation by these marrow-derived cells appears to occur through a lineage progression which is similar to that observed for embryonic tibial osteoblasts. In summary, these data support the use of diffusion chambers inoculated with avian marrow to study aspects of osteogenic and chondrogenic differentiation.

Animals↗
PubMed1990

Regenerating marrow induces systemic increase in osteo- and chondrogenesis.

Marrow ablation in long bones induces an increase in osteogenesis in distant skeletal sites. To test the role of marrow regeneration in this phenomenon, rat mandibular condyles were evaluated histomorphometrically during postablation healing of tibial marrow and after inhibition of healing. Ten days after removal of tibial marrow all bone formation parameters in the condylar subchondral bone were markedly elevated, indicating an enhanced osteoblastic activity. The thickness of the cartilaginous zone of calcification was also augmented. These changes were absent when postablation healing was inhibited in the tibia and after massive liver injury. Extensive periosteal injury induced only a slight increase in osteoblast activity. Except for a fall on day 7, the [methyl-3H]thymidine labeling index in the condylar cartilage and oral mucosa remained at control levels 3-18 days after ablation. These findings imply that stimulation of cell proliferation has only a secondary role in the skeletal response to marrow ablation. It is concluded that the systemic increase in osteogenesis occurs preferentially during marrow regeneration and is not a nonspecific skeletal reaction to tissue injury. Apparently, the systemic osteogenic response is mediated by circulating factors produced by the healing marrow; conceptually it is related to other instances where local repair in extraskeletal sites is accompanied by generalized alterations in respective tissues.

Animals↗
PubMed1989

Osteogenic response to marrow aspiration: increased serum osteocalcin and alkaline phosphatase in human bone marrow donors.

It has been shown recently in experimental animals that regeneration of bone marrow after ablation is associated with enhanced osteogenic growth factor activity and a systemic increase in bone formation. To assess the possible occurrence of a similar phenomenon in humans, serum markers of bone formation, osteocalcin and alkaline phosphatase, were measured in marrow donors before the aspiration of large amounts of iliac marrow and 1 day to 5 weeks thereafter. Both osteocalcin and alkaline phosphatase showed significant increases, with peak values 1-3 and 2-4 weeks postaspiration, respectively. The absolute maximal increase in osteocalcin was significantly higher in adolescent and child donors than in adults. When evaluated together with studies on systemic changes during fracture healing and marrow regeneration, these findings suggest that marrow aspiration in humans evokes a systemic osteogenic response.

Adolescent↗
PubMed1989

Oncogenous osteomalacia: a case study.

A case of oncogenous osteomalacia due to a fibrosarcoma of the maxilla is reported, with a 19 year course before treatment. Metabolic studies of calcium and phosphorus were performed 3 and 19 years after the first symptomology. There was a negative balance for both phosphorus and calcium with low serum levels of 1,25-dihydroxyvitamin D which were corrected by resection of the tumor. Portions of the tumor were cultured and the supernatant did not affect phosphorus transport by a proximal tubule kidney cell line. Other portions were injected into athymic nude mice where they resulted in hypophosphatemia and phosphaturia, thus confirming the endocrine nature of the oncogenous osteomalacia factor.

Adult↗
PubMed1989

Further characterization of osteogenic-cell growth promoting activity derived from healing bone marrow.

During its osteogenic phase, post-ablation regenerating bone marrow produces bone promoting activity to osteogenic cells. In the experiments reported, activity derived from (rat) healing bone marrow conditioned medium (HBMCM) after boiling was analyzed using chromatography on heparin-Sepharose. The activity in HBMCM was shown to be divided among at least six independent activities that stimulated DNA synthesis rates is osteogenic rat osteosarcoma (ROS) cells. Three activities resolved when heparin-Sepharose was washed isocratically with phosphate buffered saline. Two of these were resistant to reduction and acidification and their effect was considerably more potent in osteogenic than non-osteogenic ROS cells. Three additional activity peaks recovered when the heparin-Sepharose column was pumped with an NaCl gradient. Two of them eluted at 0.3 and 0.65 M NaCl, affected osteogenic and non-osteogenic ROS cells to a similar extent and may be attributed to platelet-derived growth factor. A third peak, resolved at 1.2 M NaCl, implies the residual activity of acidic fibroblast growth factor that persisted after boiling of the conditioned medium. It is concluded that the activity profile of HBMCM reflects the in vivo situation where the osteogenic phase of marrow regeneration is probably regulated by multiple growth factor species.

Alkaline Phosphatase↗
PubMed1988

Changes in teeth and gingiva of dogs following laser surgery: a block surface light microscope study.

The effect of laser surgery on tissues of the periodontal apparatus was studied histologically in dogs using block surface light microscopy, a novel microscopical method. With this approach, changes in the hard and soft tissue components were concomitantly demonstrated; the method enabled preservation of the in situ relationship between these components. Following laser surgery, healing in the gingiva was delayed as suggested by the presence of epithelial ulcerations and dense inflammatory infiltrate. In the enamel and cementum the application of laser resulted in crater-like defects that could be avoided only partially by insertion of a tinfoil shield into the gingival sulcus. In the vicinity of the cementoenamel junction these defects were filled with epithelium or periodontal ligament fibers; the close proximity of the hard and soft tissues at the defect sites suggested occurrence of new attachment. Enamel defects located coronal to the gingiva contained bacterial plaque. These histologic results do not demonstrate any substantial advantage of laser over conventional knife gingivectomy. Such advantage may be accomplished with the design of a special intraoral handpiece and further experiments.

Animals↗
PubMed1988

Gingivitis in the human deciduous dentition. A correlative clinical and block surface light microscopic (BSLM) study.

This study examined the relationship between clinical and histomorphometric parameters in the human deciduous dentition. Clinical parameters including plaque index, gingival swelling, gingival color, tooth mobility and degree of root resorption were determined prior to the extraction of teeth. The teeth were extracted with their surrounding gingiva in order to preserve the in situ relationship between the hard and soft tissues. Histomorphometric analysis was carried out on 55 sites, using block surface light microscopy (BSLM). Apical migration of the junctional epithelium was found at 53% (29) of the sites. The gingival sulcus was shallow (0.3 +/- 0.19 mm) and coronal to the cemento-enamel junction at 84% (46) of the sites. Junctional epithelium with retepegs was present at 89% (49) of the sites, whilst an inflammatory cell infiltrate (ICI) was present at all sites examined. The ICI was located opposite to the junctional epithelium and cementum at 80% (44) of the sites. The extent of ICI correlated positively with the patients' age and was significantly increased when clinical evidence of gingival swelling or redness was present.

Adolescent↗
PubMed1988

Regenerating bone marrow produces a potent growth-promoting activity to osteogenic cells.

It is well documented that injury to bone marrow is followed by an osteogenic phase that precedes the complete tissue regeneration. We have recently shown that postablation healing of bone marrow in rat tibiae is associated with a systemic increase in osteogenesis. It was hypothesized that a growth factor(s) with an effect on osteogenic cells is produced in the healing limb, is transferred to the blood circulation, and enhances osteogenesis systemically. To test growth factor production, healing bone marrow-conditioned medium was prepared with tissue separated from rat tibias during the osteogenic phase and assayed for enhancement of mitogenic activity in culture of osteogenic rat osteosarcoma cells (ROS 17/2). Partial purification of healing bone marrow-conditioned medium-derived growth factor(s) consisted of gel filtration on Sephadex G-25, boiling, chromatography on heparin-Sepharose, and gel filtration on Sephadex G-75. Mitogenic activity eluted in the void volume of the Sephadex G-25 column (mol wt greater than 5,000). Potent activity resolved from heparin-Sepharose with PBS, and on filtration by Sephadex G-75 this activity recovered in 3 peaks with mol wt estimates of 35,000, 19,000, and less than 10,000. The partially purified factor also showed considerable stimulatory effect on DNA synthesis in osteoblastic fetal rat calvarial cells and on in vitro elongation of fetal long bone; it had only a small effect on nonosteoblastic ROS and fetal rat calvarial cells. These data indicate that healing bone marrow produces growth factor activity with a preferential effect on osteogenic cells. It is suggested that local growth factors have a role as mediators in the sequence of events whereby bone marrow expresses its osteogenic potential. During postablation healing of bone marrow these factors may also function as systemic promoters to osteogenic cells.

Animals↗
PubMed1988

Osteogenesis in in vivo diffusion chamber cultures of human marrow cells.

The osteogenic diffusion chamber culture of rodent marrow cells is a well established system. In the present study, marrow cells from children and adult human donors were incubated in diffusion chambers implanted intraperitoneally in athymic mice. After 4 or 8 weeks, the chamber content was examined by light and electron microscopy. Child-cell cultures showed osteogenic tissue consisting of a mineralizing fibrous component and cartilage. Ultrastructurally, the fibrous tissue was similar to osteoid and exhibited osteoblast-like cells and mineralizing nodules. Mineral aggregates were also found in the cartilage. These features in child-cell chambers were similar to those found in control chambers of rabbit marrow cells. Adult-cell chambers showed only unmineralized fibrous tissue. These results render previous findings in animal-cell diffusion chamber systems relevant to the understanding of bone formation in man. It is suggested that the difference between child- and adult-cell chambers reflects an age-related decline in the number of marrow osteoprogenitor cells or their potential to undergo terminal osteogenic differentiation.

Adult↗
PubMed1988

Metabolic studies in a patient with idiopathic hypophosphatemic osteomalacia.

Studies were conducted in a patient with idiopathic hypophosphatemic osteomalacia to delineate the roles of parathyroid hormone (PTH), vitamin D and renal tubular function. A 43-year-old woman presented with progressive skeletal pains resulting in severe incapacity. Workup revealed: hypophosphatemia with a low tubular maximal phosphate reabsorption per glomerular filtrate (TmP/GFR) of 1.05 mg/dl, normocalcemia, hypocalciuria, elevated alkaline phosphatase and glycinuria. PTH and urinary cyclic AMP (UcAMP) were normal, while calcitriol was low. Renal tubular acidosis or other transport defects were not present and no tumor was found. Biopsy was diagnostic for osteomalacia, and the patient responded to 1-alpha OHD3 and phosphate therapy. Hyperparathyroidism was ruled out by 1) normocalcemia persisting after 1-alpha OHD3 and calcium loading and 2) normal PTH and UcAMP challenged by phosphate supplements. Combined calcium and 1-alpha OHD3 administration resulted in hypercalciuria, decreased UcAMP and increased, but not corrected, TmP/GFR. These findings suggest that the osteomalacia was due to hypophosphatemia caused by a renal leak. PTH is only contributory to the phosphaturia. Low calcitriol level contributes to the osteomalacia directly and indirectly through impaired mineral absorption and, therefore, is also responsible for the hypocalciuria.

Adult↗
PubMed1987

Long-term intracaval calcium infusion therapy in end-organ resistance to 1,25-dihydroxyvitamin D.

Two boys aged six and four with the syndrome of hereditary resistance to 1,25-dihydroxyvitamin D3 with rickets alopecia and growth retardation are presented. After unsuccessful therapeutic trials with pharmacologic doses of vitamin D or its active metabolites, the patients were treated by long-term intracaval infusions of calcium through an implantable catheter. A total of 0.5 to 0.9 g of elemental calcium was infused daily for 18 months and the serum calcium concentration was maintained at 9 to 10 mg/dl. Bone pain subsided within one week of treatment. Serum phosphorus, immunoreactive parathyroid hormone, and 1,25-dihydroxyvitamin D concentrations and alkaline phosphatase activity were normalized within four to nine months. Radiographs of the knees and hands revealed progressive healing of rickets with complete resolution after one year of treatment. The patients gained 12 cm and 8 cm per year in height as compared with 3 cm and 2 cm, respectively, in the previous year. A transilial bone biopsy obtained from one patient prior to treatment revealed severe osteomalacia associated with osteitis fibrosa. A follow-up biopsy examined after 12 months of therapy showed almost complete healing of osteomalacia and normal mineralization. These observations indicate the following: (1) Long-term intracaval calcium infusions are an effective mode of therapy for these patients, and (2) When adequate serum calcium and phosphorus concentrations are maintained, healing of rickets and normal growth rate could be achieved even in the absence of a normal 1,25-dihydroxyvitamin D3 receptor-effector system.

Biopsy↗
PubMed1987

Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle.

Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5-21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.

Animals↗
PubMed1987

Aluminum-related osteomalacia: clinical and histological improvement following treatment with desferrioxamine (DFO).

Aluminum-related osteomalacia has been a topic of major interest for some time. Patients on dialysis who are affected exhibit reduced parathyroid function and osteomalacia associated with high levels of aluminum in the extracellular fluid and tissues. In bone, aluminum is found in the interface between mineralized and nonmineralized osteoid. In the present study we attempted treatment of the aluminum-related bone disease with DFO, a potent chelating agent. A thyroparathyroidectomized patient on hemodialysis with proven osteomalacia and aluminum deposits in bone received DFO 3 times/week for 1 year. Consequently, there was a marked improvement in his skeletal status, both clinically and histologically. This was associated with aluminum deposits within the mineralized component of bone as well as elevated parathyroid function measured in blood and bone. These findings suggest that calcification may occur despite the presence of aluminum in the mineralizing front. The main beneficial effect of DFO could be relief of the inhibitory action of aluminum on parathyroid cells and osteoblasts.

Adult↗