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Biomedical subjects

A Ornoy

Publications and source records attributed to A Ornoy.

At least 127 records · Page 7Linked to original sources
PubMed1986

The development of fetal mice long bones in vitro: an assay of bone modeling.

This study was carried out to develop an in vitro system for the analysis of bone modeling (coincidentally occurring bone growth, formation, mineralization, and resorption) as is seen during bone development. The fetuses of pregnant mice previously labeled with 45Ca were removed on Days 15, 16, and 17 of gestation. The radii and ulnae were dissected free and cultured for up to 6 days in a chemically defined medium (BGJ) supplemented with fetal calf serum or human serum albumin and 150 micrograms/ml vitamin C. The change in bone length over the culture period was measured as were the changes in calcium and phosphorus content, the hydroxyproline: protein ratio, and the percent 45Ca released into the medium. The effect of insulin and parathyroid extract on the system was also examined. The results indicate that cultures of 16-day-old fetal bones provided the most suitable model. During culture there was a continuous increase in bone length as well as calcium and phosphorus content in the ratio of 2:1, a significant increase in the hydroxyproline content, and a continuous release of 45Ca into the medium. Parathyroid extract caused a dose-dependent inhibition of both growth in diaphyseal length and calcium and phosphorus uptake with an increase in 45Ca release into the medium. Insulin at 10(-9) M and 10(-10) M resulted in a significant increase in diaphyseal length and calcium and phosphorus uptake without affecting 45Ca release. These results indicate that the assay described is suitable for the study of bone modeling, providing a means to measure bone growth, formation, calcification, and resorption. The direct effect of various factors on bone modeling can also be measured.

Animals↗
PubMed1986

Thickness of renal glomerular capillary basement membrane in the offspring of diabetic rats fed a regular or high-sucrose diet.

Numerous animal model studies of diabetes mellitus have been reported. Diabetes-induced vascular damage is a common cause of systemic organ damage in humans and animals. Many investigations have been made of human and animal offspring of diabetic mothers. The present report documents the sequential glomerular basement membrane (GBM) thickness in fetuses and infants of diabetic rats. The postnatal increase in GBM thickness was similar in the offspring of control and diabetic rats, and was not related to the sucrose concentration in the diet.

Age Factors↗
PubMed1986

Transplacental effects of endotoxemia on fetal mouse brain, bone, and placental tissue.

Pregnant mice were given 0.005 mg endotoxin on day 10 of gestation or 0.0025 mg endotoxin on days 10 and 12. Pregnant mice treated with normal saline served as controls. On day 18 of pregnancy, fetuses and placentas were removed for microscopic and histological examination. The treated placentas had fibrin thrombi and hemorrhages in the labyrinth and spongiosa. Glycogen cells in the spongiosa were swollen. The long bones of experimental animals had few metaphyseal trabeculae, which also were disorganized, with an increase in the number of metaphyseal and diaphyseal osteoclasts. An increase in the number of necrotic neurons was observed in coronal sections of brains of experimental fetuses at the level of the trigeminal ganglion. To correlate the degree of neuronal necrosis with long-term behavioral effects, a behavioral test was performed on pups whose mothers were treated with endotoxin. The pups were tested at the age of 28 days and for the next 3 days for their audiogenic seizure response. The pups of the experimental groups were more sensitive to high sounds than the controls. Escherichia coli endotoxins seemed to have a significant teratogenic effect on mice, being more severe when endotoxin was given in divided doses to the pregnant animals. The widespread endothelial damage or the elevation of prostaglandin levels caused by endotoxins may have been responsible for these teratogenic effects.

Abnormalities, Drug-Induced↗
PubMed1986

Effects of sera from Cohen, genetically determined diabetic rats, streptozotocin diabetic rats and sucrose fed rats on in vitro development of early somite rat embryos.

The effects of sera from genetically determined Cohen diabetic rats, streptozotocin (STZ) diabetic rats and non-diabetic control rats fed a 72% sucrose diet on the in vitro development of 9 1/2 day old rat embryos from control rats have been studied. Hyperglycemic sera from diabetic rats had a high teratogenic effect: abnormalities were seen in 41.5% of embryos cultured in serum from Cohen diabetic animals and in 54% of embryos cultured in serum from STZ-diabetic rats. Malformations were seen in 25-27% of embryos cultured in serum from 2 groups of control rats fed a high sucrose diet compared with 10.7% in serum from control rats maintained on regular diet. When embryos from the experimental groups were cultured in serum from control rats on regular diet malformations were seen in 24.7% of embryos from Cohen genetically determined diabetic rats vs 10.9-12.4% in embryos from 2 non-diabetic groups. Only 14% of embryos from STZ-diabetic rats exhibited malformations when cultured in the control serum, but 42% of embryos from the same rats showed abnormalities when grown in serum from STZ-diabetic rats. Normalization of glucose level in the serum of STZ-diabetic rats by prior injection of insulin did not reduce the high incidence of malformations (51%). The high rate of embryonic malformations correlated with the ultrastructural changes of their visceral yolk sac endoderm. We suggest that serum from diabetic rats is teratogenic even at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The effects of insulin and glucose on bone modelling in vitro.

The direct effects of insulin and glucose on bone modelling was studied in an in vitro system. 16 day old mice fetal radii and ulnae prelabelled with 45Ca were cultured for 48 hr in BGJ medium supplemented with either 4 mg/ml of human serum albumin or 10% fetal calf serum. Insulin at concentrations of 10(-8)-10(-10) M induced an increase in the periosteal bone formed as well as in calcium, phosphate and hydroxyproline content. Glucose at concentrations of 200-800 mg/dl decreased bone length, calcium, phosphate and hydroxyproline content. There was no change in the 45Ca released into the medium, by either insulin or glucose, implying that these substances have no effect on bone resorption. The results of this study imply that insulin and glucose have a direct effect on bone modelling and that they may be important factors in growth disturbances occurring during diabetic pregnancy.

Animals↗
PubMed1986

The effects of maternal diabetes and high sucrose diets on the intrauterine development of rat fetuses.

The effects of streptozotocin (STZ) diabetes, genetically-determined Cohen diabetes, and of high sucrose diets on the intrauterine development of rat fetuses have been studied. The average malformation rate in 9-17-day-old embryos of STZ-diabetic rats fed a 50% sucrose diet was 10.7% and in embryos of genetically-determined Cohen diabetic rats fed a 72% sucrose diet 13.1%. When diabetic rats were fed a regular diet, the malformation rate was reduced in STZ-diabetic animals to 7% and in Cohen diabetic rats to 6.4%. The teratogenic effects of diabetes were more pronounced throughout the embryonic period (days 9-13) than during the fetal period (days 15-17). In STZ-diabetic rats the malformation rate has been reduced from 18.3% during days 9-13 to 1.6% on days 15-17 and in Cohen diabetic rats from 16.8 to 5.8%. The number of resorbed embryos was similar in both embryonic and fetal periods. The embryotoxic effects of diabetes in rats fed a regular diet were higher in Cohen diabetes than in STZ-diabetes. The high sucrose diets alone have no significant embryotoxic or teratogenic effects, but they promoted the teratogenic manifestations of diabetes. The teratogenic effects of diabetes correlated with pathological changes in the visceral yolk sac endoderm.

Animals↗
PubMed1986

Fetal outcome following primary herpetic gingivostomatitis in early pregnancy. Morphological study and updated appraisal.

Three women presented with acute primary herpetic gingivostomatitis during the first half of their pregnancy. Herpes simplex virus (HSV) was isolated by culture from the buccal lesions in two cases, and a serological confirmation of primary HSV infection was evident in the third case. One fetus, delivered during the second trimester of pregnancy, had a central nervous system anomaly, which was probably not related to the infection. The placenta exhibited mild diffuse deciduitis and focal villitis. The other two fetuses were normal and born at term. Microscopic examination of the placentas and membranes disclosed deciduitis and basal placentitis in one, which may have been caused by the herpes virus. The literature on intrauterine infection with HSV is reviewed, focusing on the significance of Type I virus as a possible teratogen. At present, there seems to be insufficient evidence to indicate pregnancy interruption following nongenital primary HSV infection in early pregnancy.

Adult↗
PubMed1985

The role of mesenchyme-like tissue in the pathogenesis of thanatophoric dysplasia.

We have studied the light microscopic, transmission, and scanning electron microscopic (SEM) findings in 13 cases of thanathophoric dysplasia (TD) and 4 control infants. In the TD growth plate, areas with less abnormal cartilage and bone alternated with areas of severely abnormal cartilage and bone. These latter abnormal areas were always found around tongues of apparent mesenchymal tissue that appeared to penetrate from the investing perichondrium and periosteum. The ultrastructure of the less abnormal areas was similar to that of the control infants, including cell and matrix structure as well as mineralization. The abnormal cartilage and bone had many ultrastructural abnormalities that were also found in the adjacent mesenchymal tissue. The mesenchymal cells, adjacent chondrocytes, and osteoblasts contained dilated endoplasmic reticulum and moderately large intracytoplasmic vacuoles. In the area adjacent to the cartilage, the matrix of the apparent mesenchyme contained thin collagen fibers and proteoglycan granules, whereas the matrix adjacent to the bone contained thick bundles of short collagen fibers. The matrix of the surrounding cartilage and bone resembled the adjacent matrix in the mesenchyme. In addition, many vesicular structures or osmiophilic particles were found in the matrix of the mesenchyme and adjacent cartilage and bone. SEM examination showed normal and abnormal bone trabeculae adjacent to each other. In the abnormal trabeculae, there were large, densely packed osteoblastic and osteocytic lacunae. The calcified collagen fibers had a random orientation, in contrast to the longitudinal orientation in the relatively normal bone. Chemical studies of collagen in the metaphyses of bones from five infants with TD showed a small amount of collagen type III (less than 5%), which was not found in three control infants. Thus, a basic pathogenetic mechanism in the skeletal abnormalities of TD appears to be the focal replacement of the growth plate and periosteum by persisting abnormal mesenchymal-like tissue from which the abnormal bone originates.

Bone Development↗
PubMed1985

Histologic and ultrastructural studies on the mineralization process in hypophosphatasia.

Chondroosseous tissue from six infants with infantile hypophosphatasia and six control infants were studied by light, transmission, and scanning electron microscopy. Alkaline phosphatase histochemical reaction of the growth plate was studied in two infants and was greatly reduced when compared to two control infants. Hypertrophic chondrocytes were increased in number with persisting cartilage islets in the metaphysis. In five of the six cases studied, chondrocytes and intercartilagenous intercellular chondroid matrix appeared ultrastructurally normal. Matrix vesicle distribution was similar to that of control subjects, but they were associated with few mineral crystals. In two infants, the matrix vesicles were alkaline phosphatase nonreactive. In the calcifying zone of the growth plate and in the newly formed metaphyseal trabecular bone, cartilagenous calcospherites often were small and the orientation of crystals was nonradial when compared to that of control infants. The mineralization of diaphyseal bone appeared normal. It seems that matrix vesicles are present in hypophosphatasia and that the impaired mineralization of cartilage is due primarily to the deficiency of alkaline phosphatase. In spite of the lack of alkaline phosphatase, secondary mineralization of bone which is not mediated by matrix vesicles was normal.

Alkaline Phosphatase↗
PubMed1985

Effects of vitamin D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats.

A model of low-phosphate, vitamin D-deficient rachitic rats was used to compare the effects of 1 alpha(OH)D3, 1,25(OH)2D3, and 24,25(OH)2D3 on cartilage and bone. The rats were maintained for 3 weeks on a high-calcium, low-phosphate, vitamin D-deficient diet, during which period they developed severe rickets. The rachitic rats were injected for 2 or 3 consecutive days with a physiologic dose of either metabolite. Other littermates were given a single dose of 50,000 IU of cholecalciferol in combination with a normal diet. Samples of cartilage fluid (Cfl) and of blood were removed prior to sacrifice for biochemical studies of some parameters of calcification. These parameters were correlated with the results of light and electron microscopic studies of the growth plate cartilage and bone. Treatment with 1 alpha (OH)D3 or with 1,25(OH)2D3, in spite of increasing Ca and P levels in the Cfl, induced only partial healing of the rickets. In contrast, 24,25(OH)2D3 or vitamin D with a normal diet resulted in complete morphologic and biochemical healing of the rickets. Transmission electron microscopic (TEM) studies have shown partial mineralization of the wide hypertrophic zone of the growth plate following treatment with 1 alpha(OH)D3 or with 1,25(OH)2D3. Mineralization was more complete with 24,25(OH)2D3 treatment. The results of this study emphasize the importance of 24,25(OH)2D3 for normal endochondral bone formation and mineralization.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

An in vitro assay of bone development using fetal long bones of mice: morphological studies.

The purpose of this study was to examine the morphological changes in an in vitro system in which the two elements of bone modelling, formation and resorption, could be studied simultaneously. Pregnant mice were killed on days 15, 16 and 17 of gestation, the fetuses were removed and the radii and ulnae dissected free of soft tissue. The bones were cultured for 6 days in media (BGJ) supplemented with 20% fetal calf serum and 150 micrograms/ml vitamin C. Growth and mineralization were estimated by measuring the total length of the bone, and diaphysis, and by light and transmission electron microscopy (TEM). The results of this study indicate that there is a continuous measurable increase in the total length of fetal mouse long bones over the 6 days of culture. These bones show a continuous growth of periosteal bone, with mesenchymal tissue penetrating into the diaphyseal shaft, and development of bone marrow like tissue. TEM examination showed differentiation of mesenchymal cells to osteoblasts, formation of new bone matrix and bone mineralization similar to that found in developmentally matched controls. In the cartilagenous epiphyses, however, many hydroxyapatite crystals were not associated with matrix vesicles. In addition, some of the chondrocytes of the hypertrophic zone appeared to be dedifferentiating into mesenchymal cells with osteoblast-like features. In spite of the lack of osteoclasts in the 15- and 16-day explants, osteoclasts appeared in the diaphysis after 2 and 4 days in culture. Our results suggest that this system can serve as a good model for the study of bone formation and resorption as they occur, simultaneously, during bone modelling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of glucose and serum from streptozotocin-diabetic and nondiabetic rats on the in vitro development of preimplantation mouse embryos.

The effects of D-glucose and serum from nondiabetic and streptozotocin (STZ)-diabetic rats on the in vitro development of preimplantation mouse embryos have been studied. It was shown that supplementation of the essential culture medium with D-glucose in concentrations of 2 to 5 mg/ml inhibited development of 43 to 74% of blastocysts in a dose-response fashion. Addition to the medium of serum from nondiabetic rats in concentrations of 10 and 20% disturbed their subsequent development in 44 and 32%, respectively. Addition to the culture medium of serum from STZ-diabetic rats in the same concentrations (10 and 20%) inhibited 53 and 54% of embryos from further development. Addition of 80% of control or of STZ-diabetic serum almost completely inhibited blastocyst development. It is suggested that both control and STZ-diabetic serum are embryotoxic to preimplantation embryos cultured in vitro. Therefore, the possible additional embryotoxic effect of STZ-diabetic rat serum on preimplantation embryos cannot be tested by this method.

Animals↗
PubMed1984

Fibrochondrogenesis: radiologic and histologic studies.

Fibrochondrogenesis is a distinct, neonatally lethal, short-limb skeletal dysplasia which was first described in a single patient in 1978. We report the radiographic and morphologic studies of 2 additional unrelated stillborn infants with fibrochondrogenesis. This syndrome has distinct radiographic and chondro-osseous morphologic defects different from those seen in the other known skeletal dysplasias. The long bones are short and dumbbell-shaped with metaphyseal flare. The spine is platyspondylic with superior-inferior clefting defects, and the ribs are short and distally cupped. The growth-plate cartilage is grossly disorganized and has a densely fibrous collagenous matrix when examined by light and electron microscopy. Light, transmission, and scanning electron microscopy shows diaphyseal and metaphyseal trabecular bone to be normal.

Abnormalities, Multiple↗
PubMed1984

Effects of interferon and encephalomyocarditis virus on in vitro development of preimplantation mouse embryos with and without the zona pellucida.

Development of preimplantation mouse embryos, with or without the zona pellucida, in the presence of interferon (IFN) and mouse encephalomyocarditis (EMC) virus was studied using the in vitro culture method. The embryos (2- to 8-cell stages) were obtained from superovulated mice and cultured in modified Witten's medium under paraffin oil in 5% CO2 in air at 37 degrees C. Removal of the zona pellucida does not affect the subsequent development of the embryos: 90% of embryos with and 87% of embryos without the zona pellucida reached the morula-early blastocyst stages. Mouse IFN (10(4) units/ml) had no inhibitory effect on the developmental ability of the preimplantation embryos with or without the zona pellucida: 88 and 89% of the embryos in each group, respectively, reached the morula-early blastocyst stages. The preimplantation mouse embryos were sensitive to the embryotoxic effect of EMC virus: at a multiplicity of 20 infection particles per embryo the development of 43% of embryos was inhibited. The zona pellucida had no significant protective effect: Its removal changed only slightly the susceptibility of the preimplantation embryos to this virus. Pretreatment of embryos with IFN did not protect them from the embryotoxic effect of EMC virus. This work indicates that preimplantation mouse embryos appear to be resistant for both the antiviral and antiproliferative activities of IFN.

Animals↗
PubMed1984

Ultrastructural studies of initial stages of mineralization of long bones and vertebrae in human fetuses.

We studied 27 embryos of 5-12 weeks gestational age where pregnancy was interrupted due to paramedical reasons, in order to find the developmental stages at which matrix vesicles appear in cartilage, and whether they are involved in the mineralization process. Specimens of long bones, lumbar and thoracic vertebral column were prepared for light, transmission and scanning electron microscopic studies. In the cartilaginous models of long bones, matrix vesicles were found amongst maturing and hypertrophic chondrocytes already by the 6th week after fertilization. By that stage, bone rudiments consisted of only cartilage that was not yet mineralized. In the vertebral column matrix, vesicles were found in the vertebral bodies amongst maturing and hypertrophic chondrocytes at the beginning of the 8th week. At that stage, although hypertrophy of chondrocytes was observed, mineralization was still absent. No matrix vesicles were found in the perichondrium, investing mesenchyme and intervertebral discs. Mineralization of cartilage in long bone rudiments started in the form of hydroxyapatite crystals within or around the matrix vesicles at 7 weeks of age and in the vertebral column at 11 weeks. As mineralization progressed, more hydroxyapatite crystals were observed around the matrix vesicles, forming typical calcospherites . Mineralization then progressed in the form described in other animals.

Bone Matrix↗