Biomedical subjects

J E Aaron

Publications and source records attributed to J E Aaron.

At least 19 recordsLinked to original sources

PubMed1994

The cryomicrotomy of rat dental tissues: a technique for histological and immunohistochemical analysis.

We have applied a method developed for the cryomicrotomy of non-decalcified bone to the histological preparation of the tooth and related dental tissues. Cryosections of rat mandible have been cut on a heavy-duty freezing microtome. Both cellular and extracellular structure was well preserved and the sections of tooth and bone appeared to be suitable for optical and scanning electron microscopy and for immunohistochemical analysis. However, there was an overall strong non-specific binding of immunohistochemical reagents to enamel which was not evident in the other mineralized tissues of the mandible. This may relate to important differences in the nature of this tissue.

Ameloblasts↗

PubMed1992

Paleohistology of Paget's disease in two medieval skeletons.

Paget's disease has been ascribed several times to specimens of archeological bone but, in the absence of microscopic examination, the evidence remains insubstantial. Suspected metabolic bone disease is described here in the archeological remains of a skeleton from a 16th century burial ground at Wells Cathedral, England and from a single medieval sacrum recovered from a large deposit of disarticulated bones from a churchyard at Barton-on-Humber, England. Radiographs showed apparent structural abnormality in one femoral shaft and calcaneus and in the isolated sacrum. Histomorphometry on undecalcified bone cores confirmed the regions of abnormality and showed not only increased trabecular width but also areas of "mosaic" woven bone together with extensive resorption cavities; these features contrasted with the normal structure and organized lamellar bone from sites elsewhere. Despite post-interment changes in surrounding tissues, the morphological stability of some of the osteocytes was remarkable. Preservation of the histology was sufficient to permit the assignment of a metabolic bone disorder and the nature of the sclerosis was consistent with Paget's disease.

England↗

PubMed1992

Trabecular generation de novo. A morphological and immunohistochemical study of primary ossification in the human femoral anlagen.

An understanding of trabecular formation in early skeletal development may provide insight into the problem of trabecular replacement in the aging skeleton. In an optical and scanning electron microscope study of the processes of de novo trabecular generation, the immunohistochemical distribution of collagen Types I, II and III, together with the matrix organising proteins fibronectin and tenascin, has been examined in the ossifying human femoral anlage. In the region of the developing spongiosa, the primary osseous trabeculae that arose by endochondral ossification were assembled around calcified cartilage remnants, consisting almost entirely of aggregates of mineralised microspheres. These structures were specifically recognised by antibodies raised against collagen Type II and fibronectin. In contrast, the primary osseous trabeculae that arose by subperiosteal intramembranous processes, were assembled around a framework of prominent coarse fibres that were recognised by antibodies raised against collagen Type III and tenascin. Irrespective of their origin, all the new trabeculae were similar in their general staining character for collagen Type I and fibronectin. However, throughout the developmental stages examined here endochondral trabeculae were separated from intramembranous trabeculae by a discrete boundary of compressed cells and mineralised cartilage.

Bone Development↗

PubMed1992

An automated method for the analysis of trabecular bone structure.

Trabecular structure as well as bone mass is important in studies of bone disease and fracture. An automated method for the direct analysis of two-dimensional trabecular micro-anatomy and its application to human iliac crest bone biopsies is described. Compared with established methods which require expensive equipment and complex software, costs have been reduced and availability increased by using an image analyzer driven by a microcomputer. Routine histological sections are accepted and an editing function enables the removal of artifacts. An elastic window allows field expansion for large specimens. The program enables the rapid assessment of the bone volume and trabecular surface from the intact image, followed by image skeletonization and the deduction of the trabecular length, number, character, and spacing together with the number of trabecular junctions and discontinuities; the trabecular width is calculated indirectly. Images may be stored to disk or printed as permanent records for diagnostic or research purposes.

Biopsy↗

PubMed1992

Bone hypertrophy and trabecular generation in Paget's disease and in fluoride-treated osteoporosis.

The replacement of lost trabeculae characteristic of postmenopausal osteoporosis is problematic, since a biological pathway has not been established for trabecular regeneration de novo in the healthy, intact, mature skeleton. Possible pathways for trabecular replacement may occur under pathological conditions, in particular those associated with bone hypertrophy. The topography of trabecular hypertrophy was compared in two groups of subjects with disease- or treatment-induced osteosclerosis following a period of atrophy. In Paget's disease and fluoride-treated osteoporosis a thickening of rarefied trabeculae in both was associated in Paget's disease only with an increase in the trabecular number and the transformation of a discontinuous arrangement into a more continuous network. The sequence seems to be a progression of intratrabecular resorption normally attendant upon a period of trabecular thickening. The failure of fluoride-treated bone in this respect, due to the unusual stability of the fluorotic skeleton, may provide insight to more effective anabolic regimens.

Adult↗

PubMed1992

Parathyroid gland hormones in the skeletal development of the ovine foetus: the effect of parathyroidectomy with calcium and phosphate infusion.

It has been confirmed that the foetal parathyroid glands are important in development and that thyroparathyroidectomy (TXPTX) of the ovine foetus with thyroxine (T4) replacement leads to hypocalcaemia, retarded skeletal development, depressed calcification and rickets, relative to thyroidectomy plus T4 replacement. Histomorphometric and biochemical (urinary excretion of deoxypyridinoline) indices of bone resorption are also reduced. However, skeletal calcification can be restored to normal by long-term infusion of the TXPTX foetuses with phosphate and calcium sufficient to normalise the plasma Ca2+ x Pi ion product. Nevertheless, depressed resorption, reduced osteoblast numbers and delayed development persisted. The evidence suggests that the abnormally low number of resorption cavities and osteoclasts may result from the reduction in circulatory parathyroid-hormone-related protein consequent upon the removal of the foetal parathyroid glands and that this hypercalcaemic factor has a direct effect upon the process of resorption and primary trabecular remodelling of the foetal skeleton.

Amino Acids↗

PubMed1992

Osteoporotic fractures: an unusual presentation of haemochromatosis.

The association of haemochromatosis and osteoporosis is well established, but it is unclear whether this is due to iron overload, hypogonadism, liver disease, or diabetes mellitus. We describe a young eugonadal male patient with osteoporotic fractures as a presenting feature of haemochromatosis, suggesting that factors other than hypogonadism contribute to osteoporosis.

Adult↗

PubMed1991

The effect of sodium fluoride on trabecular architecture.

The effect of sodium fluoride therapy on iliac trabecular bone has been studied in 15 patients with primary osteoporosis by comparing bone biopsies taken before and after two years of treatment. A marked increase in bone volume (43%) was observed, which was attributable to an increase in trabecular thickness (46%) rather than their number. Because the trabecular bone surface, the trabecular number, the bone volume/trabecular width ratio, and the trabecular terminus number do not change significantly after fluoride treatment, we conclude that fluoride does not induce the de novo generation of trabeculae, nor does it restore trabecular connectivity despite the restoration of bone mass. These data suggest that the restoration of skeletal mass with fluoride may not lead to a comparable decrease in the risk of future fracture.

Adult↗

PubMed1991

Immunolocalization of collagen types I and III, tenascin, and fibronectin in intramembranous bone.

Structural components of the organic bone matrix were located by immunohistochemical techniques in fresh-frozen sections of normal and dysplastic bone. Fine and coarse birefringent fibers were identified as separate and distinctive features in the extracellular matrix by antibodies raised against human collagen Type III. The glycoprotein tenascin was located on a proportion of the fibers in a characteristic beaded pattern, which was absent in dysplastic bone. The fibers originated in the periosteum or in the fibrous stroma of the marrow cavity and were oriented with regard to both the spatial and the lamellar organization of the bone. The disposition and composition of the fibers suggests that they form a preliminary framework on which intramembranous bone modeling proceeds, and that the specific location of tenascin on the fibers in normal developing membrane bone may be important in determining the alignment of the bone tissue. Epitopes recognized by the collagen Type I and fibronectin antibodies were demonstrated throughout the mineralized matrix, but their incorporation into the collagen "Type III" fibers was evident only outside the mineralized matrix.

Antibodies↗

PubMed1990

Bone loss and age-related fractures.

The aging of the skeleton represents an important cause of both morbidity and mortality in the Western World. A great deal is known about the epidemiology, pathogenesis, and structural alterations which occur during the osteoporotic process to increase the risk of fracture with age. Whereas osteoporosis is associated with a decrease in bone mass, factors other than bone mass are clearly important. These include the turnover of bone and the destruction of trabecular elements, the repair of fatigue damage, as well as extraskeletal factors. An improved understanding of the aging of bones will form a basis for improved strategies for its prevention and treatment.

Age Factors↗

PubMed1989

Secondary osteoporosis and the microanatomy of trabecular bone.

Osteoporosis is a generic term implying a decrease in bone mass which increases the risk of fracture. It is now becoming appreciated that decreases in bone mass alone are not the sole factor in increasing the risk of osteoporotic fracture, and that other skeletal and extraskeletal factors also contribute significantly to this risk. Extraskeletal factors include the propensity to falls and responses to falls, whereas additional skeletal factors include bone turnover, the ability to repair fatigue damage and the tertiary structure of bone, particularly trabecular tissue. There are a large number of causes of secondary osteoporosis each with their own specific pathophysiological mechanisms. It is therefore not surprising that they have heterogeneous effects on the skeleton. A good example is provided in corticosteroid osteoporosis which is characterised by thinning of trabecular elements, whereas postmenopausal osteoporosis is characterised less by thinning and more by destruction of trabecular elements which derange trabecular continuity. A variety of techniques are now being developed to address the heterogeneity of trabecular osteoporosis. These include direct histomorphometric techniques to assess trabecular continuity, and indirect techniques such as the attenuation of ultrasound. These different pathophysiological mechanisms in osteoporosis have important therapeutic implications, particularly with agents that affect bone remodelling. Since bone remodelling is a surface-based phenomenon, if trabecular surfaces are destroyed, the augmentation of bone mass may thicken remnant structures without restoring trabecular continuity. Since most treatments for osteoporosis affect bone remodelling they are likely to have a greater effect in restoring structural integrity of the skeleton in corticosteroid than in postmenopausal osteoporosis.

Adrenal Cortex Hormones↗

PubMed1989

Histomorphometry of fresh frozen iliac crest bone biopsies.

Although methods are well established for the rapid histological preparation of fresh frozen soft tissues, they remain inadequate for the preservation of hard tissues. A recent technique for sectioning fresh frozen bone, in which sections can be prepared within an hour, has been applied to undecalcified human iliac crest bone biopsies. Quantitative analysis has shown that the static remodeling variables deduced from frozen sections closely resemble those derived from plastic-embedded sections prepared for routine use by established laboratory procedures. It is concluded that the rapid method is reliable for immediate diagnostic and histomorphometric purposes.

Biopsy↗

PubMed1989

Spinal osteoporosis in men.

In 94 men with crush fracture, 40 were found to have primary osteoporosis. Cross-sectional measurements of a number of variables related to bone in these 40 patients were compared to the values in various groups of healthy men aged 20-96. In healthy men, metacarpal and femoral cortical area/total area, bone volume, osteoid surfaces, seam and trabecular width, plasma dihydroepiandrosterone and estrone, and radiocalcium absorption fell with age, whereas eroded surfaces, trabecular number, urine hydroxyproline and calcium/creatinine ratios, plasma alkaline phosphatase, estradiol, androstenedione, cortisol and testosterone remained constant with age. As compared with healthy men, men with primary osteoporosis had reduced femoral cortical area/total area (P less than 0.05), and Singh grade (P less than 0.001) and in seven there was a history of forearm or femoral fracture. On iliac crest biopsy, bone volume (P less than 0.001) and trabecular number (P less than 0.01) were decreased. Plasma alkaline phosphatase (P less than 0.02) was increased but urine hydroxyproline and calcium excretion were not significantly raised. Calcium balance was negative due to failure of absorption to match urinary calcium loss and radiocalcium absorption (P less than 0.01) and plasma 1,25-dihydroxyvitamin D (P less than 0.05) were reduced.

Adult↗

PubMed1989

The parathyroid glands in the skeletal development of the ovine foetus.

The ionized plasma calcium concentration in foetal lambs during the last third of gestation is greater than that in the ewe. Since foetal plasma immunoreactive parathyroid hormone is less than that in the ewe the role of the foetal parathyroid glands is not clear. The effects of foetal parathyroidectomy (PTX) on the foetal:maternal gradient and on skeletal development are examined. The histomorphometry and ash content of six PTX lambs was compared with that of 11 intact animals. A reversal of the plasma ionized calcium gradient took place within 3 days without significant change in the foetal plasma inorganic phosphate or 1,25-dihydroxycholecalciferol content. Skeletal changes consistent with rickets were observed and increased in severity with the time after PTX. It is concluded that the foetal parathyroid glands play an important role in placental calcium transfer and skeletal calcification. However, the agent may be a hypercalcaemic substance other than parathyroid hormone.

Animals↗

PubMed1989

Contrasting microanatomy of idiopathic and corticosteroid-induced osteoporosis.

Previous studies of microanatomic changes in normal bone with age have suggested that underlying differences in bone remodeling between male subjects and female subjects give rise to different patterns of bone loss. The relationship between microanatomic and histologic levels of organization are herein examined in two groups of osteoporotic subjects, one with idiopathic and the other with corticosteroid-induced osteoporosis. Using tissue from the iliac crest, total trabecular surface and trabecular width and number were measured, together with bone volume and static and dynamic indices of formation (osteoid surface, seam width, mean wall thickness, lamellar thickness, calcification fronts, and mineralization rate) and resorption (total resorption cavities and osteoclast incidence). The results suggest that while a similar loss of trabecular bone volume is common to both groups, there is a marked distinction in the distribution of the remaining bony tissue and indices of remodeling. A decline in trabecular number accompanied by a relative increase in resorption characterized both sexes with primary osteoporosis, whereas a decline in trabecular width associated with depressed formation was the predominant feature in the secondary disease. Thus trabecular attenuation is principally the manifestation of depressed formation, while trabecular discontinuity is primarily the manifestation of bone resorption.

Adrenal Cortex Hormones↗

PubMed1988

Bone histology and mineral homeostasis in human pregnancy.

Mineral homeostasis was studied biochemically and histologically in patients in early pregnancy and at term. In early pregnancy there was evidence of increased and reversible resorption of bone, whereas in late pregnancy bone demonstrated active formation and rapid mineralization with minimal resorption. Gut absorption of calcium was not increased in early pregnancy. The overall findings were consistent with calcium liberation from bone in early pregnancy, and with enhanced conservation of bone calcium at term. It is proposed that the additional calcium required during pregnancy is derived largely from the skeleton during early gestation and from dietary absorption at term.

Adult↗

PubMed1987

Rapid preparation of fresh-frozen undecalcified bone for histological and histochemical analysis.

An increasing need to be able to relate hard tissue morphology to its histochemistry, and the lack of an adequate methodology, prompted this investigation of polyvinylpyrrolidones of varying chain length as supporting films for the cryomicrotomy of fresh undecalcified cortical and trabecular bone. We developed a method that parallels histological procedures but is biochemically inert and functions at -25 degrees C. Using an LKB heavy-duty cryomicrotome, large numbers of serial sections suitable for histochemistry, immunocytochemistry, or rapid histology can be prepared with ease. Sections from mouse skull, ox vertebra, and human iliac crest illustrate the versatility of the method, and have been examined for the preservation of general morphology and of histochemical activity of those enzymes most prominent in remodeling. The procedure does not preclude the subsequent application of standard hard-tissue embedding methods to the remaining material. Comparison with plastic-embedded bone shows not only close similarities in the structural preservation of the frozen tissue, making possible histomorphometry, but also shows some interesting staining differences. These include the absence of differentiation of the calcification front with toluidine blue stain in fresh frozen specimens, and the presence in frozen osteoid tissue of specific methylene blue metachromasia missing from plastic preparations.

Acid Phosphatase↗

PubMed1987

The microanatomy of trabecular bone loss in normal aging men and women.

Histomorphometric changes in normal bone were investigated using tissue from the ilium of 86 women and 98 men, aged 20-90 years. While loss of trabecular volume was common to both sexes, the histologic basis for the loss differed. Decreased formation (expressed primarily as static indices) seemed to be the principal factor in bone loss in men; in women these features remained unchanged, suggesting that increased resorption was the principal factor. Bone loss in women was principally attributable to the total removal of individual trabeculae; conversely in men, there was generalized attenuation of trabecular bone. Similar findings in bone tissues of vertebral bodies suggest that differences in bone remodelling between the sexes produce different patterns of bone loss as a sequence of aging.

Adult↗