Biomedical subjects
Publications and source records attributed to M M Silver.
This appears to be the first reported case of membranous glomerulonephritis in a pediatric asymptomatic carrier of hepatitis B virus in North America. Routine immunofluorescent methods were used to identify the hepatitis B surface antigen in glomeruli. In addition, the glomerular immune deposits were searched for the known ultrastructural forms of the virus.
We have presented the unique clinical and morphological features of 3 patients with an imperforate tricuspid valve and right ventricular tensor apparatus. Thus, despite valve tissue and apparatus, there was not a perforate atrioventricular connection. This most uncommon type of tricuspid atresia' was associated in all 3 cases with a congenitally absent pulmonary valve, an underdeveloped right ventricle, and a curious distortion of the ventricular septum. Indeed, 2 of these patients demonstrated severe disproportionate ventricular septal thickening, although histopathologic examination did not substantiate those features usually associated with a hypertrophic cardiomyopathy. Rather, microscopic examination revealed a sinusoidal malformation consisting of normal myocardial cells separated by branching ethothelial-lined channels which communicated with the right ventricular cavity. In addition, gross examination of these 3 specimens revealed an abnormally persistent right venous valve in 2, which subdivided the right atrium. Finally, these cases provide further evidence that the term 'tricuspid atresia' oversimplifies the observed morphological features.
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Two male fetuses (18 and 22 weeks gestation) and a 3-month-old male infant (full sibling of the younger fetus) who were diagnosed with Walker-Warburg syndrome (WWS) on the basis of neuropathologic autopsy findings in brain, eyes, and muscle also had micro-orchia and, microscopically, diffuse gonadoblastoid dysplasia in the testes. Both fetuses also had a miniature left ureter and cystic dysplastic left kidney. Testes from control fetuses of 17-24 weeks gestation with normal karyotype and no central nervous system abnormalities (group A, n = 50), a variety of central nervous system abnormalities (group B, n = 50), or an autosomal aneuploidy syndrome with or without central nervous system abnormalities (group C, n = 30) had no diffuse dysplasia, although a single gonadoblastoid seminiferous tubular profile was present in three controls. Testicular morphology was normal in older fetuses and infants with a wide variety of central nervous system malformations (group D, n = 50). We found no evidence of hypogonadotrophic hypogonadism in the three WWS cases to account for the small penis and incompletely descended testes commonly reported in this condition. We concluded that the apparent specificity of the gonadoblastoid testicular dysplasia to WWS suggests that the gene defect directly affects testicular development.
A simple method is described for the isolation of trophoblast cells from both first trimester and term placenta. Trophoblast preparations were characterized by light microscopy, scanning and transmission election miscroscopy and immunohistochemistry to distinguish these cells from mesenchyme and endothelium. Trophoblast cells were cultured on various substrates and a comparison made of their ability to attach, proliferate and function. A collagen gel substrate produced by repolymerization of an acid soluble collagen fraction from chorionic villi allowed rapid attachment of trophoblast cells and maintainance of their original morphology. Term trophoblast cells were shown to become fully functional in short term (three day) cultures by virtue of their increased immunocytochemical staining for the presence of beta hCG, hPL and SPI. beta hCG increased significantly by day three thus demonstrating functional activation. Trophoblast cells from first trimester placenta formed proliferating colonies of hormone producing cells while those from term placenta reaggregated into clusters and closely resembled syncytiotrophoblast both morphologically and functionally. This short term culture system for term trophoblast will allow further studies into the biology of trophoblast polypeptide hormone synthesis and secretion.
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Immunogold ultrastructural localization of chromogranin A in secretory granules within tumor cells provides convincing evidence of endocrine or neuroendocrine differentiation. A modified immunogold method (designed for use on osmicated tissue) produced positive labeling of small granules not only in well-differentiated tumors but also in poorly differentiated small cell tumors primary in lung, cervix, and skin; only a proportion of granules in some of the tumor cells were positively labeled. Many non-small cell lung tumors often stain focally positive for chromogranin A at the light microscopy level, and such tumors may also contain sparse, small, dense granules. Because positive labeling could not be demonstrated over small granules in non-small cell lung tumors, the theory that such tumors are neuroendocrine in type may be erroneous.
A mildly macerated, hydropic fetus was delivered spontaneously at 25 weeks gestation by a multigravidous black mother. At autopsy, gross and microscopic evidence suggested fetal anemia, and excessive extramedullary erythroblastosis was present generally. Erythroid precursor cells in the pulmonary capillary circulation contained eosinophilic nuclear inclusions consistent with human parvovirus B19 infection. Transmission electron microscopy on osmicated Epon lung sections showed lucent, granular chromatin corresponding to the inclusions. In rare foci only these sections contained paracrystalline arrays of 20-nm virions. In the same cells, similar virions were seen within the cytoplasm, both randomly distributed and in paracrystalline aggregates. Postembedding immunoelectron microscopy, done on formalin-fixed lung embedded in a hydrophilic resin, showed positive labelling over the nuclear inclusions, and also localized the viral capsid antigen to cytoplasmic virion aggregates. The nuclear aggregates suggest that the virus would reach the circulation after cell lysis whereas those in cytoplasm suggest that parvovirus also may be excreted from infected cells before they lyse.
Two different effects of maternal autoantibodies presented in a third-trimester pregnancy. The first was complete fetal heart block, demonstrated ultrasonographically, which correlated with the presence of anti-Ro and anti-La antibodies in the maternal serum. The second effect was decidual vasculopathy and thrombosis, a morphologic finding in the placenta that caused massive placental infarction and intrauterine death. The placental pathology correlated with the presence of anticardiolipin antibodies in the maternal serum at the time of stillbirth.
Three unrelated female term infants died when less than 1 month old from intractable pulmonary hypertension associated with deficient capillaries in airspace walls, anomalous small pulmonary veins in bronchiolar-arterial rays, and medial thickening in small pulmonary arteries together with peripheral muscularization. This complex vascular abnormality in the lungs has been termed alveolar capillary dysplasia and/or misalignment of lung vessels in seven previously reported cases. Each infant also showed abnormally immature parenchymal development in the lungs, as was noted in four of the seven prior cases. One had phocomelia; four of the seven prior cases had a variety of congenital anomalies. The primary pulmonary vascular anomaly is likely to be a failure of fetal lung vascularization dating from the second trimester and to be due to action of an unknown teratogen. Centroacinar veins may represent bronchial veins that do not normally develop beyond the ends of cartilaginous bronchi. Pulmonary arterial occlusive changes are interpreted as reactive to obstruction at the level of pulmonary arterioles.
To learn whether fetal congestive heart failure causes a characteristic tissue iron storage pattern, we selected 15 neonatal autopsy cases of hydrops fetalis in which both the clinical and gross autopsy findings suggested intrauterine congestive heart failure. The latter appeared to be due to functional causes in 10 (3 nonhemolytic anemia, 4 cardiac dysrhythmia, 3 dilated cardiomyopathy) and was associated with cardiac malformation in 5. We graded the amount of hepatocellular siderosis, reticuloendothelial siderosis, and renal tubular siderosis in Perls-stained microscopic sections of liver, spleen, and kidney and compared the iron storage pattern with that in 15 normally developed neonatal autopsy controls (4 preterm, 11 term) and a further 7 with hemolytic anemia (5 alpha-thalassemia, 2 parvovirus B19 infection). Liver cell siderosis was absent in the three cases with nonhemolytic anemia. It was increased in 11 of the remaining 12 cases, as in hemolytic anemia controls. Among the five cardiac malformation cases, three had proximal renal tubular siderosis (as in hemolytic anemia controls) attributed to turbulent blood flow through the heart. Among the five, hydrops appeared to be due to prenatal closure of the foramen ovale in one and to prenatal constriction of the ductus arteriosus in another. In one of the five, and despite complex malformation of the heart, hydrops appeared to be due to complete heart block. We concluded that, although clinical information and morphologic assessment of the heart were basic to identifying a cardiac cause of fetal hydrops, histologic assessment of the pattern of iron storage helped confirm the pathologic diagnosis. Analysis of the pathologic findings led to a scheme for categorizing cardiogenic fetal hydrops.
Alveolar capillary dysplasia, a rare cause of neonatal pulmonary hypertension characterized by a developmental abnormality in the pulmonary vasculature, was diagnosed by lung biopsy in a male newborn maintained on nitric oxide therapy for 18 days. Autopsy confirmed the pulmonary vascular defect and demonstrated deficient airspace formation. In addition, a bronchial generation count was low, suggesting that the abnormal lung vascular development in this condition represents a special form of pulmonary hypoplasia that starts in early fetal life.