Comparison of the effects of cortisone acetate on calcification, ossification, and resorption of fetal mice long bones--in vivo and in vitro studies.
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Animals↗
Biomedical subjects
A Ornoy
Publications and source records attributed to A Ornoy.
Ultrastructural evidence of long-lasting cerebellar degeneration after early exposure to phenobarbital in mice.
Previous studies in this laboratory demonstrated a 20 to 30% reduction in cerebellar Purkinje and granule cells after exposure to phenobarbital (PhB) early in life. Therefore, neurons in the cerebellar cortex were examined for signs of cytologic degeneration using transmission electron microscopy (TEM) after exposure to PhB pre- and postnatally. Pregnant mice were given the acid form of PhB in their milled food (3 g/kg, gestation days 9 to 18) and water, ad libitum. Neonates were injected s.c. with an aqueous solution of sodium PhB (50 mg/kg body weight), days 2 to 21 after delivery. Controls were fed regular food or injected with the vehicle. The offspring were anesthetized on day 14 or 50 by an acute overdose of PhB and immediately perfused with a formaldehyde-paraformaldehyde or glutaraldehyde solution. The pyramis vermis of the cerebellar cortex was excised and processed routinely for TEM. The three layers of the cortex were examined. A short-term effect (at day 14) was found. More significantly, the treatment appeared to establish or trigger a degenerative process, the results of which were still apparent at day 50, more than 30 days after the termination of PhB treatment. Using double-blind evaluation for the presence and frequency of abnormalities, the cerebellar neurons of treated animals had 155 to 300% more abnormalities compared with control animals. Abnormalities included (i) Mitochondrial degeneration, ranging from swelling, collapse of cristae, vacuolization, to total granularization; (ii) lamellar bodies distributed throughout the cytoplasm and in cell processes; and (iii) myelin sheath degeneration, including periodic swelling and collapse, twisting of the coat, and scattered, unevenly stained areas. Damage was usually focal. Affected cells were found adjacent to normal cells in all areas of the cortex. PhB may cause the neural damage through a possible hormonal role.
Animals↗
Clinical heterogeneity in a sibship with Niemann-Pick disease type C.
The clinical presentation of Niemann-Pick type C is variable. However, in families hitherto described, the affected individuals in a given sibship show a similar clinical course. A family with histological and biochemical findings of Niemann-Pick type C is described. Four of the affected siblings presented with an early onset and a fulminant course resembling Niemann-Pick type A, whereas in the fifth sibling a later onset and a much slower neurological deterioration was observed. Genetic counseling in families with Niemann-Pick type C should take into consideration the possibility of clinical heterogeneity within the same sibship.
Fibroblasts↗
Mucolipidosis IV: prenatal diagnosis by electron microscopy.
Mucolipidosis IV (ML IV) is a lysosomal storage disease presenting in infancy with cloudy cornea and psychomotor retardation. Our experience with 12 pregnancies at risk for ML IV, monitored by transmission electron microscopy (TEM) studies of cultured amniotic fluid cells, is presented. The prenatal diagnoses were confirmed in the 3 affected and the 8 unaffected pregnancies. In the one pregnancy where no definite diagnosis was reached the pregnancy was terminated. TEM examination of fetal tissues from this pregnancy showed no abnormal lysosomal storage bodies and a review of the cultured amniotic fluid cell sections revealed that the diagnosis of a normal fetus could have been made.
Adult↗
Teratogenicity of bromocryptine in pregnant rats.
The teratogenicity of bromocryptine (CB-154, Sandoz, Basel) was studied in three groups of pregnant rats which received 0.625 mg/kg/day, 1.25 mg/kg/day, and 2.5 mg/kg/day bromocryptine, respectively, i.m. and in a control group of pregnant rats which received the solvent only. There was no significant difference in the birth rate, fetal resorption rate, male/female ratio and malformation rate between the four groups. There was a significant elevation of the average fetal and placental weights between the experimental and the control fetuses. Bromocryptine does cross the placental barrier and in our study might act as growth promoting factor.
Abnormalities, Drug-Induced↗
Prenatal diagnosis of ataxia telangiectasia.
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Adult↗
Placental and fetal pathology in infectious mononucleosis. A possible indicator for Epstein-Barr virus teratogenicity.
Placentae and membranes were studied microscopically in five cases of pregnancy interruption due to maternal infectious mononucleosis in the first 2 months of pregnancy. This viral disease, caused by Epstein-Barr virus and apparently rare in pregnancy, induced specific placental lesions. In the decidua, these lesions were manifested by perivasculitis and necrotizing deciduitis. The membranes exhibited slight to moderate chorionitis. In the villi, endovasculitis, perivasculitis, and occasional vascular obliteration were found, as well as mononuclear and plasma cell villitis, with many large atypical vacuolated cells resembling plasma cells. Three fetuses were studied, two of which exhibited myocarditis. The fact that there were placental lesions in all cases studied, and that two of the fetuses exhibited myocarditis, must stimulate further research concerning the possible teratogenicity of this virus in man.
Abortion, Therapeutic↗
Placental changes as a consequence of the interruption of midtrimester pregnancies by prostaglandin F2 alpha. A study of 23 cases.
Placentae from 23 patients whose midtrimester therapeutic abortions were induced by the prostaglandin (PG) F2 alpha were examined microscopically. In a majority of the cases, the predominant finding was severe decidual necrosis. Different quantities of edematous villi, with or without congestion, containing swollen stromal Hofbauer cells, were found along with trophoblastic necrosis and subchorionic intervillous thrombosis. The amniotic epithelium, however, had usually not degenerated in spite of the intraamniotic injection of PGF2 alpha. These findings were compared with the histological findings described in placentae from 18 cases of midtrimester spontaneous abortions with normal fetuses. It seems that prostaglandins used in midtrimester abortion affect the placental membranes to a lesser degree than do hypertonic solutions. These findings might explain the fewer maternal complications in PGF2 alpha midtrimester abortions. The significance of decidual changes and their role in the production of maternal complications is unknown.
Abortion, Induced↗
Placental findings in spontaneous abortions and stillbirths.
Placentae and membranes of 360 spontaneous abortions and stillbirths were studied by light microscopy and compared to 100 induced abortions of 2-5 months gestation. The placental findings were correlated with morphological and chromosomal studies of the fetuses. A high incidence of hydatid degeneration was found in early spontaneous abortions (less than 12 weeks of age), especially in "blighted ova." "Atypical" stromal cells were found in the placental villi of early abortions with trisomy and triploidy. In late spontaneous abortions (13-18 gestational weeks) inflammatory lesions of the placentae were observed in over a third of cases and the incidence of hydatid degeneration was very low. The incidence of inflammatory lesions of the placentae was further raised in cases of early fetal death (18-24 gestational weeks), involving 60% of the placentae of fetuses without malformations. In stillborn infants, over 25 weeks of age, the incidence of inflammatory placental lesions dropped again, and the incidence of vascular lesions was raised to 50%. It seems that inflammatory lesions of the placentae may play an important role in the etiology of midtrimester spontaneous abortions. Isolation of the infectious microorganism and subsequent treatment may therefore reduce the rate of fetal losses in this group.
Abortion, Induced↗
Transplacental effects of cortisone acetate on calcification and ossification of long bones in mice.
The transplacental effects of cortisone acetate on the skeleton of neonatal mice has been investigated. Pregnant mice were injected intramuscularly with 0.75 mg cortisone acetate daily on days 11-19 of gestation. The mice were allowed to deliver and pups were weighed on days 1, 3, 5, 10, 15, 20 and 30 and compared to controls. Light microscopy of non-decalcified longitudinal sections of bones revealed mineral precipitates throughout the zone of hypertrophic cartilage most prominent on days 1, 3 and 5 and gradually disappearing on days 10-20. Transmission electron microscopy revealed intracellular calcification of maturing and hypertrophic chondrocytes in addition to abnormal calcification of the interstitial substance. Hydroxylapatite crystals were not necessarily associated with matrix vesicles. Scanning electron microscopy of long bones revealed a wide zone of calcified intercartilagenous matrix representing the calcified proliferating and hypertrophic zones. In this area, the calcospherites varied in size (0.5-1.4 mu in diameter) and were found in both longitudinal and transverse septa. No significant differences in the distribution and shape of cartilage matrix vesicles between experimental and control animals was observed. However, the fact that mineral crystals in experimental animals was not necessarily associated with matrix vesicles points to the possibility that this "pathological calcification" may utilize a different mechanism than the normal process through matrix vesicles.
Animals↗
Prenatal diagnosis of Fanconi anemia.
Prenatal diagnosis was performed on a fetus at risk for Fanconi anemia. A high spontaneous (0.30 breaks/cell) and diepoxybutane-induced (0.69 breaks/cell) chromosome breakage rate indicated an affected fetus and the pregnancy was terminated. The anatomic findings in the aborted fetus together with cytogenetic findings in cultured fetal skin fibroblasts confirmed the prenatal diagnosis.
Abnormalities, Multiple↗
Transplacental effects of 1,25-dihydroxycholecalciferol and of 24,25-dihydroxycholecalciferol on the limb skeleton of fetuses and offspring rats.
The transplacental effects of 1,25(OH)2D3 and of 24,25(OH)2D3 on bone formation in rat fetuses and pups have been investigated. Pregnant rats treated with 1,25(OH)2D3 or with 1,25(OH)2D3 and 24,25(OH)2D3 showed hypercalcemia, while those treated with 24,25(OH)2D3 did not. Fetal weight was markedly reduced by treatment with 1,25(OH)2D3 and not with 24,25(OH)2D3 or with a combination of both metabolites. Microscopical examination of fetal long bones showed after treatment with 1,25(OH)2D3 a marked reduction in diaphysial length. Diaphyseal trabeculae were thin and disorganized. The epiphysis had a thinner layer of hypertrophic and calcified cartilage. The numbers of osteoclasts in the diaphysis and metaphysis were the same as in controls. Treatment with 24,25(OH)2D3 did not affect fetal bone length; many bone trabeculae were found in the diaphyseal cavity leaving small bone marrow spaces; the number of osteoclasts in the metaphysis and in the diaphysis was increased. All changes in the skeleton disappeared during the first week after birth. It can be suggested that high doses of 1,25(OH)2D3 inhibit bone formation and maturation of cartilage. The addition of 24,25(OH)2D3 to 1,25(OH)2D3 seemed to reduce the toxic effects of the latter on the fetal skeleton. These results point to a definite difference between the action of high doses of 1,25(OH)2D3 and 24,25(OH)2D3 on fetal bone.
24,25-Dihydroxyvitamin D 3↗
Pneumoscrotum complicating percutaneous liver biopsy.
Pneumoscrotum developed after percutaneous liver biopsy in a 5-yr-old boy. Fifteen minutes after the procedure an enlargement of the right scrotum was noted. X-rays revealed a very small right-sided pneumothorax, subcutaneous air dissecting along the right chest and right abdominal walls and a confluent pocket of air in the right scrotum. We suggest that the air from the pleural cavity penetrated the superficial fascia in the upper right abdomen and dissected beneath the deep membranous layer into the scrotum.
Biopsy↗
Asymmetry and discordance for congenital anomalies in conjoined twins: a report of six cases.
Six pairs of conjoined twins have been studied. The first case was a pair of 13-week-old omphalopagus fetuses. One was a holoacradius amorphus and the other had rachischisis and anencephaly. The second case was a pair of omphalopagus twins. One of the twins was macerated and corresponded to a developmental age of 13-14 weeks, while the other was developed to 28-30 weeks of gestation and exhibited urogenital and gastrointestinal defects not found in the smaller twin. In the third case, that of a thoracoomphalopagus, one had cleft lip and palate, pulmonic stenosis, and atresia of the ileocecal valve, while the other did not show these anomalies. In the fourth cae, also omphalopagus twins, one had a lumbosacral meningomyelocele and severe gastrointestinal and urogenital anomalies not found in the second twin. The fifth case was a pair of thoracoomphalopagus twins, sharing a common heart with asymmetrical anomalies. The sixth case was a diprosopus anencephalic conjoined twin. The first pairs of conjoined twins were discordant for several abnormalities in nonshared organs, in addition to having abnormalities of the conjoined organs. It seems that discordance in conjoined twins is not a rare finding. The factors that play a role in discordance of anomalies in conjoined twins are probably similar to the factors in monozygotic twins--i.e., environmental, genetic, and abnormal placental and/or fetal circulation.
Abnormalities, Multiple↗
Influence of tetracycline on the calcification of epiphyseal rat cartilage. Transmission and scanning electron-microscopic studies.
Tetracyclines are known to interfere with bone calcification. We therefore studied their effects on matrix vesicle production and initial calcification of cartilage. 15-day-old rats were injected intraperitoneally with oxytetracycline 100 mg/kg, 6 consecutive injections every 12 h. Epiphyseal plates were examined by scanning and transmission electron microscopy and compared to light microscopy findings. It was found that high doses of tetracyclines cause degeneration of the chondrocytes in the proliferating and hypertrophic zones. Chondrocytes had short processes with only few matrix vesicles covering their surface. In the chondrocytic lacunae of the longitudinal septa of hypertrophic and calcifying cartilage there were fewer matrix vesicles as compared to controls, and their ability to aggregate and form mineralized calcospherites was impaired. This was further proven when bones were immersed in 7% NaOCl or ashed, as minerals containing calcospherites were hardly seen. It is therefore presumed that interference with intracellular and probably extracellular accumulation of calcium by tetracycline might inhibit matrix vesicle production and aggregation, thus inhibiting calcification.
Animals↗
Ultrastructural studies on the origin and structure of matrix vesicles in bone of young rats.
Tibiae of young rats were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in order to study the origin and structure of matrix vesicles in periosteal bone. SEM studies have shown that periosteal osteoblasts have elongated processes with globular structures of 0.1 micron in diameter attached to the cell surface and processes. Similar structures were found to cover the inner surface of osteoblastic lacunae. The SEM studies have further shown that in the periosteal surface (forming bone) the above-described globules once mineralized, aggregated to form larger, nonhomogeneous mineralized spherules in which, by proper treatment with NaOCl, hydroxyapatite crystals could be exposed. Endosteal osteoblasts had fewer processes, devoid of the globular structures. Similarly, osteocytic and osteoclastic processes, although elongated and numberous, were not covered by the globular structures. In the matrix, collagen fibers of forming bone were randomly orientated, while in the deeper areas of bone they formed bundles with a longitudinal orientation. TEM studies have shown that the structures found on the osteoblastic surface and in the matrix are membrane-bound matrix vesicles which seem to be formed by budding from cell processes. Preformed membrane-bound vesicles were also observed by TEM inside sections of osteoblastic processes. These vesicles resembled the extracellular matrix vesicles in size and shape, thus giving the impression that at least some of the matrix vesicles are preformed cellular structures. While comparing SEM with TEM, it can be conducted that in bone, as in cartilage, matrix vesicles which probably serve as the initial locus of calcification, are formed directly by osteoblasts.
Animals↗
Extramembranous pregnancy: maternal, placental, and perinatal implications.
The case of a patient who survived extramembranous pregnancy is presented, and the maternal, fetal, placental, and neonatal features of the condition are described and delineated. Previously underscribed phenomena include clinical evidence of fixed fetal position and a unique pattern of hemosiderin and hematoidin staining of the fetal membranes. The patient described had an intermediate form of the oligohydramnios tetrad following premature rupture of the membranes; the infant survived with respiratory support therapy in spite of apparent partial lung hypoplasia. On the basis of this and previous observations of the outcome of pregnancy complicated by prolonged amniotic fluid leakage, preliminary recommendations for the management of such pregnancies are made.
Abruptio Placentae↗
Teratogenic effects of sucrose diet in diabetic and nondiabetic rats.
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Abnormalities, Drug-Induced↗