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PubMed1999

Fetal lactic dehydrogenase variation in normal pregnancy and in cases of severe intra-uterine growth restriction.

Physiological and pathological fetal levels of lactic dehydrogenase (LDH), including its five different iso-enzymes are still poorly known. Our objectives were to compare total LDH levels and its five iso-enzymes between a control group of healthy fetuses and a group of fetuses with severe intra-uterine growth restriction (IUGR), and to determine the biochemical associations and the prognostic value of elevated LDH activity in fetuses with IUGR. Total LDH levels, haematologic values and liver enzyme activities were measured in 108 healthy fetuses from 17 to 37 weeks of gestation and in 44 fetuses with severe IUGR. Total fetal LDH in plasma from the healthy fetuses were constant throughout pregnancy (mean (SD)= 305.09 (46.97)). Total LDH values in plasma significantly increased in cases of IUGR (p=0.003), and the degree of increase was significantly correlated with fetal erythroblastosis (n =44, r=0.80, p<0.001). LDH 5 significantly decreased in the IUGR group (p=0.03). Total LDH values strictly above 400 IU/l (a value equal to the mean+2 SD in the healthy fetus group) were found to be significantly associated with thrombocytopenia (p<0.001), erythroblastosis (p=0.008) and an increase in AST value (p=0.03). These results suggest that the fetal LDH value in plasma is a useful biological marker for severe chronic distress.

Case-Control Studies↗
PubMed2001

Fetal and embryonic hemoglobins in erythroblasts from fetal blood and fetal cells enriched from maternal blood in fetal anemia.

BACKGROUND AND OBJECTIVES: To determine whether there is a delay or reversal in switch mechanisms from embryonic (e and z) to fetal (g) hemoglobins accompanying the erythroblastosis of anemic fetuses and whether an increased erythroblast count in fetal blood is associated with an increase in feto-maternal cell trafficking. DESIGN AND METHODS: Fetal and maternal blood samples were obtained from 10 cases with rhesus isoimmunization and 2 cases with maternal Parvo-B19 virus at 19-33 weeks' gestation. Blood samples were also taken as controls from 61 fetuses and 86 mothers. Fetal erythroblasts were isolated by triple density gradient centrifugation and magnetic cell sorting with CD71 antibody. Fluorescent antibodies were used to immuno-stain for zeta (z), epsilon (e) and gamma (g) hemoglobin chains. In the maternal samples, fluorescence in situ hybridization (FISH) for X and Y chromosomes was also carried out to confirm the presence and proportion of the enriched fetal cells from maternal blood. RESULTS: In both fetal and maternal blood the percentage of erythroblasts positive for g-globin chain was significantly higher in the anemic fetuses compared to the controls (fetal blood, p<0.001, R=0.91; maternal blood, p<0.001, R=0.56), but there was no significant difference in expression of the e and z-chains. The percentage of cells with Y-signals was also higher in the maternal samples of anemic fetuses compared to normal controls (p<0.001, R=0.56). INTERPRETATION AND CONCLUSIONS: These findings suggest that the erythroblastosis of anemic fetuses is not accompanied by a delay or a reversal in switch from embryonic to fetal hemoglobin chains. Severe fetal anemia is associated with an increase in feto-maternal cell trafficking.

Adult↗
PubMed1992

Characterization of an angiosarcoma-inducing mutation in the erbB oncogene.

The erbB oncogenes of two transducing viruses that arose in chicken 5005 have been molecularly characterized. One of these viruses, AEV-5005, caused erythroblastosis. The other, AAV-5005, caused angiosarcoma. Both viruses had identical 5' junctions of viral and host sequences, indicating that both arose from the same proviral insertion. The erbB oncogenes of both viruses encoded transmembrane, kinase and C-terminal domains of the chicken epidermal growth factor receptor. The C-terminal domain of the AEV-5005 erbB was complete, whereas that of AAV-5005 contained a 59 amino acid internal deletion (amino acids 993-1051 of the chicken epidermal growth factor receptor). Oncogenicity tests using retroviral constructs containing the erbB sequences from AEV-5005 and AAV-5005 demonstrated that both erbB genes caused erythroblastosis and that the 59 amino acid deletion conferred the ability to induce angiosarcoma. The 59 amino acid deletion also caused increased levels of erbB autophosphorylation in cells grown in the presence of sodium orthovanadate.

Amino Acid Sequence↗
PubMed1992

[Post-gastrectomized vitamin B12 deficient anemia with marked leukoerythroblastosis and ringed sideroblasts].

A 77 year-old man, who had received total gastrectomy and splenectomy 11 years ago for gastric cancer was transferred to our hospital because of severe macrocytic anemia. He had been treated with vitamin B1, B2, C and iron preparations for several weeks. Ten days before admission numbness developed in his legs. On physical examination he appeared severely anemic. Laboratory findings revealed severe macrocytic anemia with poikilocytosis, anisocytosis, polychromasia, red cell fragmentation, Howell-Jolly bodies, Cabot rings and marked erythroblastosis (421/100 WBC). Hypersegmented neutrophils and immature granulocytes were also seen in the blood. The bone marrow picture showed marked erythroid hyperplasia, but erythroblasts revealed only slight megaloblastic changes. On bone marrow iron staining all erythroblasts were classified as type III sideroblasts and 15% of them were ringed-form. Serum vitamin B12 was low (44 pg/ml). Methylcobalamin given intramuscularly led to the rapid improvement of all hematological abnormalities including leukoerythroblastosis. Two weeks after vitamin B12 administration, ringed sideroblasts could no longer be detected in the bone marrow. Post-gastrectomy vitamin B12 deficiency anemias combined with erythroblastosis and ringed sideroblasts is a rare condition. Splenectomy is thought to play an important role in the pathogenesis of these conditions.

Aged↗
PubMed1990

Six amino acids from the retroviral gene gag greatly enhance the transforming potential of the oncogene v-erb-B.

Avian erythroblastosis virus (AEV) induces both erythroblastosis and fibrosarcomas in susceptible birds and transforms the corresponding cells in culture. Neoplastic transformation by AEV is mediated principally by an oncogene known as v-erb-B. We have explored the means by which this gene is expressed from the genome of AEV and uncovered an important structural determinant for the potency of the oncogene. In order to define the boundaries of v-erb-B and the supplementary oncogene, v-erb-A, we sequenced all but a small portion of the genome of the ES4 strain of AEV. We then demonstrated that, during expression in infected cells, splicing fuses the first six amino acids of the retroviral gene gag to the body of the v-erb-B protein. In order to explore the impact of this fusion on the function of v-erb-B, we constructed vectors with Murine Leukemia Virus that express the oncogene either with or without the fusion to gag. Viruses generated from these two vectors differed greatly in their abilities to transform cells: fusion of v-erb-B with gag enhanced its transforming ability 50 to 100-fold as determined by focus transformation assays and growth in soft agar. Our data suggest that the difference in transforming ability is not due to alterations in transcription or translation but, rather, may result from changes in post-translational modification.

Amino Acid Sequence↗
PubMed1989

[Retroviruses with 2 oncogenes].

Less than a decade ago, some acute transforming avian leukemia retroviruses that transduced not one but two distinct cellular genes that could cooperate in the viral-proned transformation processes was discovered. In this paper three examples of such retroviruses are presented. This are: avian erythroblastosis virus ES 4 (AEV-ES 4), avian erythroblastosis virus E 26 (AEV-E 26), avian Mill-Hill-2 myelocytomatosis virus (MH 2).

Alpharetrovirus↗
PubMed1989

[Ultrasonic monitoring of intravascular transfusion in severe Rhesus incompatibility. Diagnostic and therapeutic aspects after fetal relaxation].

Since October 1985 47 ultrasound-guided intrauterine intravascular transfusions were performed in 14 patients at the Department of Obstetrics and Gynecology of the University of Ulm. All newborns were delivered in good condition. The successful diagnostic and therapeutic management of severe erythroblastosis in a twin pregnancy is described. The twin with severe signs of erythroblastosis had an initial hematocrit of 12% at 26 weeks of gestation. Intravascular transfusion of 60 ml packed red cells raised the hematocrit to 41%. The ascites disappeared completely ten days after the first transfusion. Two further transfusions were performed at 29 and 33 weeks of gestation. The intrauterine intravascular relaxation with Norcuron (Vecuroniumbromid) has proved advantageous in preventing interfering fetal movement. Both newborns were delivered in good condition at 36 weeks of gestation.

Acute Disease↗
PubMed1985

[A member of the SRC gene family, the c-erbB-1 gene, is closely related to the EGF receptor gene].

An avian erythroblastosis virus, AEV-H, induces both erythroblastosis and sarcomas in susceptible chickens. Since AEV-H carries the v-erbB as a sole oncogene, the erbB gene was suggested to be responsible for the induction of these tumors. Analysis of the amino acid sequence predicted from the nucleotide sequence of the v-erbB gene revealed that the gene product has a domain characteristic for tyrosine kinase. Recently in has been suggested has the v-erbB protein is a part of the chicken EGF (epidermal growth factor) receptor. Using antibody against either v-erbB protein or EGF receptor, we also demonstrated close similarity between the two proteins. Further studies on human genomic DNA revealed that the c-erbB-1 gene, a proto-oncogene of the v-erbB gene, is the EGF receptor gene. We were also able to identify the c-erbB-2 gene that seems to code for a EGF receptor-like protein with a domain for tyrosine kinase. Finally, we would like to show that cell lines established from human squamous cell carcinom are frequently associated with amplification of the c-erbB-1/EGF receptor gene.

Alpharetrovirus↗
PubMed1987

Haematological and pathomorphological studies on chickens inoculated with transformation-defective sarcoma virus.

A transformation-defective mutant of Rous sarcoma virus (td PR-RSV-C) inoculated into chicken embryos caused a number of pathological changes in chickens after hatching. Disturbances in haematopoiesis were manifested by anaemia of different degree and by the presence of immature blood elements in the peripheral blood. The haematological picture of erythroblastosis was confirmed histologically. In addition to erythroblastosis, lymphoid leukosis and a proliferative lymphosarcoma-like tumour were demonstrated histologically.

Animals↗
PubMed1980

In vivo effect of three transformation-defective mutants of subgroup C avian sarcoma viruses.

Three transformation-defective mutants derived from avian sarcoma viruses of subgroup C, td PR-RSV-C (Vogt), td B77 (Toyoshima) and td daPR-RSV-C (isolated in our laboratory), were injected intravenously into 12-day-old chicken embryos and intraperitoneally into newly-hatched chickens. Both Brown Leghorn chickens and F1 hybrids of two inbred chicken lines (C X I) were used. Haematological changes and formation of visible tumours were evaluated in animals kept for 8-9 months. All three td mutants produced in a significant proportion of intraembryonally injected animals haematological disorders which, in certain cases, resembled the anaemic and proliferative type of erythroblastosis. Most conspicuous symptoms of erythroblastosis were seen after td daPR-RSV-C which also gave rise to two sarcomas, containing transforming viruses. The possible character of oncogenic information retained or acquired by the TD mutants is discussed.

Anemia↗
PubMed1995

Preliminary study of oncogene expressions in endometrial cancers. Aberrant estrogen receptor gene and erbB-2 expressions.

We studied the expressions of aberrant epidermal growth factor receptor (EGFR) gene or erbB-2, which is highly homologous to EGFR gene, and erbA or estrogen receptor (ER) gene, which is highly homologous to erbA, as a preliminary study, to know which oncogene expressions are associated with the development of endometrial cancers. ErbB-2 mRNA lacked only extracellular domain (EX), suggesting the lack of downregulation of erbB-2 expression by a ligand, which led to regulated tyrosine kinase activity. Mutated DNA binding domain of ER mRNA were found in 3 of the 13 cases, suggesting the promotion disorder of estrogen-inducible proteins in these 3 endometrial cancers. The behavior of aberrant erbB-2 and ER gene co-expressions is considered of similar to that of erbA and erbB co-expressions in the chicken introduced by the avian erythroblastosis virus, which leads to the development of erythroblastosis in the chick, and seems to be associated with the development of endometrial cancer.

Adult↗
PubMed1995

Vaccination with a low-oncogenic strain of Rous sarcoma virus prevents visceral tumors in chickens.

The oncogenic potential of different strains of Rous sarcoma virus (RSV) varies significantly in two Mhc(B) congenic chicken lines CB and CC and in their F1 hybrids with the unrelated inbred line IA. The Bryan high-titer pseudotype of RSV of antigenic subgroups D and B (BH-D, and BH-B) was highly oncogenic, eliciting mostly fatal, progressively growing tumors. Visceral tumor formation and erythroblastosis were seen after challenge with BH-B in CB and CC chickens, but not in their F1 hybrids with IA. Tumor regression induced by a low-oncogenic RSV strain PR-C elicited a protective immunity capable of preventing not only the progressive growth of challenge tumors at the site of inoculation, but also visceral tumor formation and erythroblastosis.

Animals↗
PubMedDate not supplied

Ultrasound in the evaluation and management of the isoimmunized pregnancy.

Real-time ultrasound was a valuable adjunct in the management of 57 consecutive isoimmunized pregnancies. The pathophysiology of hydrops fetalis as it affects the sonographic anatomy of the fetus and placenta is discussed. Real-time ultrasound was slightly more accurate than amniotic fluid bilirubin analysis in predicting moderate to severe erythroblastosis fetalis. The most useful finding was a disproportionate growth of the fetal abdominal circumference in relationship to the biparietal diameter. Ultrasound proved invaluable in several difficult situations, such as contaminated amniotic fluid, ruptured membranes, and twins. Suggestions for the further quantitation of this diagnostic test are explored.

Adult↗
PubMed1983

Fetal blood group studies during mid-trimester pregnancy and the management of severe isoimmunization.

Fetal blood samples collected at 14-22 weeks' gestation by fetoscopy have been analysed for 25 different red cell antigens and anti-A antibodies. The results obtained demonstrate that the technique can be used to determine fetal blood groups during mid-pregnancy and also to provide the opportunity to study the physiological and pathological developments of blood groups and their antibodies and to manage more rationally those pregnancies threatened by erythroblastosis fetalis.

Antibodies, Anti-Idiotypic↗
PubMed2001

[Blueberry muffin baby: the pathogenesis of cutaneous extramedullary hematopoiesis].

Two neonates exhibited the clinical picture of the "blueberry muffin baby" at delivery. The integument manifested petechiae and purpuric magenta-colored macules, papules, and plaques, as well as blueberry-colored ecchymoses. These findings led to the diagnosis of a connatal cytomegalovirus infection and fetal erythroblastosis, respectively. The hemorrhagic-purpuric looking skin lesions reflected extramedullary hematopoiesis with ultrastructural study disclosing evidence of both erythro- and granulopoietic lineage. For the first time, we were able to demonstrate that complexes of red cells in various stages of maturation can occur in the skin, similarly to the erythroblastic islands of the bone marrow. In the pathogenesis of extramedullary hematopoiesis, mechanisms underlying the reconstitution of blood cells must be considered. These may reactivate hematopoiesis in organs where it previously occurred in embryonic and fetal life. Possible causative factors may be great compensatory demand, deficient replacement, or loss or dysfunction of corpuscular blood elements. This would explain the occurrence of this disease entity in conjunction with etiologically completely heterogeneous systemic diseases.

Cytomegalovirus Infections↗
PubMed1975

The significance of meconium staining.

Meconium staining of the placenta and/or fetal body was present at birth in 10.3 per cent of 42,000 live-born infants, but present disproportionately in 18.1 per cent of 788 neonatal deaths. The neonatal mortality rate was 3.3 per cent in the stained group and 1.7 per cent in the nonstained group. Among infants who died, the incidence of erythroblastosis was quadrupled and that of cardiovascular malformation was doubled in the stained group. Meconium staining was associated with a decrease in the expected frequency of hyaline membranes and atelectasis even in premature infants; hypotheses for this phenomenon were presented. Meconium staining of the fetus or placenta requires several hours of exposure. As a hypothesis, the observed increase of deaths in stained neonates may be related to the stresses of cumulative or chronic hypoxia which may occur after the initial passage of meconium if delivery is prolonged.?23AUTHOR

Amniotic Fluid↗
PubMed1975

Cord blood coagulation studies in infants of high-risk pregnant women.

A prospective study of cord blood for coagulability, evidence for disseminated intravascular coagulation (DIC), and hematocrit was done in 106 infants who were offspring of mothers with high-risk pregnancies (pre-eclampsia, diabets mellitus, third-trimester bleeders, severe erythroblastosis fetalis, maternal hypertension, fetal distress, and spontaneous premature labor). Significant changes of hypercoagulability (low AT-III and abnormal TEG) were seen in the third-trimester bleeder and premature labor groups which also had the highest incidence of IRDS and necrotizing. Infants undergoing "stress" (pre-eclampsia, fetal distress) had elevated levels of factors V and VIII but were not hypercoagulable or AT-III deficient. Except for mild thrombocytopenia, infants of the diabetic mothers, a group with increased thrombotic complications, did not show any cord blood abnormalities. Offspring of third-trimester bleeders were anemic. The EBF infants were also anemic, severely hypercoagulable, and showed coagulation changes compatible with severe liver disease and/or DIC. Mild changes compatible with intravascular coagulation were seen in six infants and were not related to the the development of IRDS.

Antithrombins↗
PubMed1977

Ultrasound as an aid in intrauterine transfusion.

Although the number of patients with Rh isoimmunization in pregnancy has been decreasing in recent years, intrauterine transfusion is still an important form of therapy for those patients whose infants have erythroblastosis. We have used both gray-scale and real-time ultrasonography for the last ten cases in which intrauterine transfusion was necessary. These techniques were used in preference to fluoroscopy and x-ray control to identify the placental site and fetal abdomen and to direct the insertion and placement of the transfusion needle. We were able to visualize the needle when it entered the amniotic cavity and the fetal abdomen. The technique afforded continuous visualization and a cross-sectional image of the fetus, steps which increase the efficiency and safety of the procedure and decrease radiation to the fetus.

Blood Transfusion, Intrauterine↗