Biomedical subjects
E S Gray
Publications and source records attributed to E S Gray.
Regulation of hepatic growth hormone receptors in coho salmon (Oncorhynchus kisutch).
Factors potentially regulating hepatic growth hormone (GH) receptors in coho salmon (Oncorhynchus kisutch) have been investigated. From December to June of the first year, relative changes in hepatic 125I-sGH binding and 35SO4 incorporation by ceratobranchial cartilage were similar. Stunted salmon, which in seawater have elevated plasma GH yet fail to grow, showed lower hepatic 125I-sGH binding than did normally growing seawater salmon. However, MgCl2 treatment of stunts' membranes to reveal total specific binding of 125I-sGH indicated receptor occupation by endogenous sGH. Total specific 125I-sGH binding was low in seawater stunts and remained low if these fish remained unfed after return to fresh water, but increased approximately twofold upon feeding. Total specific binding in fasted salmon in fresh water showed a trend toward decreased levels by 1 week; by 3 weeks, binding was 40% lower than in fed fish. There was a positive correlation (r = 0.600) between condition factor and total specific binding in fed and fasted salmon in fresh water. Two weeks after hypophysectomy total specific binding was 50% lower than in sham-operated control salmon, indicating pituitary regulation of GH receptors. GH treatment reduced both free and total 125I-sGH binding in salmon examined 24 hr after treatment. Treatment with recombinant bovine insulin-like growth factor I, thyroxine, or cortisol did not affect free 125I-sGH binding. Both the pituitary and nutrition appear to be prime regulators of hepatic GH receptors in coho salmon.
Parvovirus infection of the human fetus and newborn.
Human parvovirus B19 is a recently recognized cause of hydrops fetalis. It is a small, single-stranded DNA virus, which preferentially infects late erythroid precursors and produces red blood cell (RBC) aplasia, fetal anemia, and cardiac failure. Infection is accompanied by characteristic intranuclear inclusions in fixed and circulating RBC precursors. These inclusions have been shown to contain virus particles by electron microscopy and in situ hybridization. Infection of the fetus, mother, and newborn infant can be diagnosed by serological and molecular methods selected to match the stage of the infection. Recent work has shown that parvovirus B19 can infect cells other than erythroid precursors, and that additional mechanisms such as myocarditis may contribute to hydrops fetalis in some cases. Infected fetuses are not always hydropic. Maternal infection results in increased abortion and stillbirth even in the absence of transplacental transmission, which occurs in approximately one third of infected mothers. The overall risk of fetal loss following maternal exposure is much less than previously thought, and may be less than 3% in the first 20 weeks of gestation or approximately 10% if the mother is actually infected. Although parvoviruses are teratogenic in animals, there is no evidence that B19 is a significant teratogen in man. The long-term outlook of survivors of intrauterine infection, including those successfully treated by intrauterine blood transfusion, appears to be good, but requires further study.
Dandy-Walker malformation in the Meckel syndrome.
The Meckel syndrome is an autosomal recessive condition and includes a heterogeneous group of CNS malformations, most frequently occipital encephalocele. We report on 2 sibs and one other unrelated case with Meckel syndrome in whom the CNS anomaly was the Dandy-Walker malformation, an association not previously described. The criteria used to diagnose the Meckel syndrome are also reviewed.
Sex differences in hepatic monooxygenases in winter flounder (Pseudopleuronectes americanus) and scup (Stenotomus chrysops) and regulation of P450 forms by estradiol.
Details concerning the endogenous regulation of hepatic cytochrome P450 monooxygenases in teleosts, and the features of this regulation common among fish species, are poorly known. Gonadally mature female winter flounder (Pseudopleuronectes americanus) have been reported to have severalfold lower levels of microsomal cytochromes P450 and b5 and NADPH-cytochrome c reductase than do males (Stegeman and Woodin ('84) Mar. Environ. Res., 14:422-425). These strong sex differences prompted more detailed study of P450 regulation in winter flounder liver, and a comparison with sex differences in another marine teleost, scup (Stenotomus chrysops). Ethoxyresorufin O-deethylase (EROD) activity/nmol P450 was less in gonadally mature females than in males of both species. Immunoblot analysis with MAb 1-12-3 to P450E (the EROD catalyst) showed that the content of P450E counterpart was also much less in females of both species. Aminopyrine N-demethylase (APND) and testosterone 6 beta-hydroxylase (6 beta-OHase) activities per nmol P450 were higher in gonadally mature female than in mature male flounder, differences not seen in scup. Polyclonal antibodies to scup P450A were shown to detect proteins in a number of teleosts. The levels of anti-P450A cross-reacting protein were greater in mature female than in male flounder, but as with 6 beta-OHase activity, the content of this protein was not sexually differentiated in scup. Estradiol treatment of winter flounder depressed the rates of EROD, APND, 6 beta-OHase, and estradiol 2-OHase activities per mg protein, but APND and 6 beta-OHase activities per nmol P450 were unchanged. Thus, E2 promotes general decreases in some hepatic P450-catalyzed activities, but in achieving sex differences there is also specific regulation of the P450E counterpart, and possibly of the 6 beta-OHase (P450A?). Other factors, temporal or hormonal, can modify the effect of E2 treatment, and may contribute to the specific regulation of P450 forms in naturally maturing fish, and to species differences in this regulation.
Apparent Fryns' syndrome and aneuploidy: evidence for a disturbance of the midline developmental field.
A premature male infant is described in whom the presence of coarse facies, diaphragmatic hernia, genital anomalies and Dandy-Walker malformation suggested a diagnosis of Fryns' syndrome. Lymphocyte karyotype revealed a partial trisomy 22, and his mother carried an apparently balanced 11/22 translocation. Three infants have been described recently with features of Fryns' syndrome and various aneuploidies. It is suggested that amplified developmental instability of the midline developmental field may account for some of the phenotypic resemblances between these cases.
Growth regulation in the gobiid teleost, Gillichthys mirabilis: roles of growth hormone, hepatic growth hormone receptors and insulin-like growth factor-I.
Studies of the teleost Gillichthys mirabilis were undertaken to assess the role of GH in regulating hepatic GH receptors, insulin-like growth factor-I (IGF-I) activity and cartilage growth. Hypophysectomized G. mirabilis were injected with saline vehicle or with 10, 100 or 1000 ng tilapia GH (tGH)/g every other day for 2-3 weeks. Growth, judged by increased body weight and length, was inhibited by hypophysectomy and stimulated by increasing tGH doses. Hepatic GH receptors, measured by 125I-labelled tGH binding, were decreased 50% by hypophysectomy. An additional dose-dependent reduction in binding was observed 24 h after tGH injection, but MgCl2 stripping of membranes suggested receptor occupation by exogenous tGH. IGF-I activity, measured by 35SO4 incorporation into oral cartilage explants in vitro, was decreased 50% by hypophysectomy and increased to 200% of intact control levels after injection of 1000 ng tGH/g. In a second experiment, 35SO4 incorporation by oral cartilage from hypophysectomized fish injected with 10, 100 or 1000 ng tGH/g was stimulated to intact control levels. Effects of feeding and tGH injection on in-vitro responsiveness of oral cartilage to recombinant bovine IGF-I (rbIGF-I; 10-1000 ng/ml) were also assessed. Oral cartilage from fed fish showed a parabolic dose-response curve, whereas oral cartilage from starved fish had a lower basal rate of 35SO4 incorporation and a linear dose-response relationship. Oral cartilage from hypophysectomized G. mirabilis showed a significantly attenuated response to rbIGF-I which was restored by tGH injection, suggesting that the GH status of the animal is important for sensitivity of target tissue to IGF-I. Because of its similarity to other vertebrate systems, G. mirabilis presents a good teleost model of growth regulation and of the functions and interactions of GH and IGF-I.
Radioreceptor assay for growth hormone in coho salmon (Oncorhynchus kisutch) and its application to the study of stunting.
Binding sites for native chum salmon growth hormone (sGH) in coho salmon (Oncorhynchus kisutch) hepatic membranes were analyzed by radioreceptor assay. Displaceable (specific) binding represented up to 25% of total radiolabeled sGH added. Binding was dependent on buffer pH and membrane protein concentration, and was complete by 24 hours at 15 degrees C. Specific binding was greatest in liver membranes, and was also detected in muscle, ovary, gill, kidney, and brain. Scatchard analyses indicated a single class of hepatic binding sites that were specific for sGH. In stunts, abnormal seawater salmon with elevated plasma GH levels and inhibited growth, specific binding of sGH to liver membranes was three times lower than in normal seawater smolts. The concentration of salmon GH binding sites was decreased in stunt livers by 60%, while their affinity for sGH was unchanged. Down-regulation of hepatic GH receptors by high plasma GH levels may explain in part the low sGH binding in stunts.
Neonatal xanthogranulomatous pyelonephritis.
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Unilateral cystic disease of the neonatal kidney: a rare presentation of tuberous sclerosis.
Two renal lesions have been described in tuberous sclerosis, angiomyolipomas and cysts. We report a newborn male infant in whom massive cystic enlargement of one kidney was the first manifestation of the disease.
Primitive neuroectodermal tumor.
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Mesoblastic nephroma and non-immunological hydrops fetalis.
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Paravertebral neuroblastoma in a macerated fetus.
A retroperitoneal neuroblastoma (primitive neuroectodermal tumour) occurred in a macerated male fetus of 15 weeks' gestation. Such tumours are rare but probably not as uncommon as the few published case reports imply. In view of the recent conflicting reports on the significance of such cases, the importance of this abnormality is discussed. We conclude that histological examination can exclude the possibility of traumatic artifact.
Human parvovirus and fetal anaemia.
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Human parvovirus infection in pregnancy and hydrops fetalis.
Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.
Human parvovirus infection.
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Parvovirus infections in pregnancy.
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Cytogenetic analysis in 100 spontaneous abortions in North-East Scotland.
The results of an extremely detailed cytogenetic analysis on 100 spontaneous abortions occurring in the Aberdeen area over a 3 year period is presented. A comparison with other published series reveals that there is a higher culture success rate (93%) accompanied by a lower incidence of trisomy and a higher incidence of triploidy, although the percentage of chromosomally abnormal foetuses in first trimester abortions is comparable with other studies. However, these apparent discrepancies can largely be explained on the basis of gestational age and sampling variation.