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[Fractionation of human erythrocytes according to their sedimentation behaviour caused by gravity. II. Application for the differential diagnosis of erythroblastosis caused by incompatibility in the abo blood group system (author's transl)].

In contrast to Rh-erythroblastosis the diagnosis of A/B0-erythroblastosis by means of serological methods is often impossible. Further biochemical investigations, the demonstration of elevated erythrocyte sedimentation rates in polyvinylpyrrolidone and of typical microsphaerocytes in blood smears can support the diagnosis. Using a modified method by Danon et al. the authors demonstrate an additional population of heavy erythrocytes in the blood of patients suffering from A/B0-erythroblastosis, the relative amount of which correlates with the severity of the disease. The fast method seems to permit prognostic predictions in cord blood.

ABO Blood-Group System↗

Obstetrical problems coincidental to intrauterine transfusion for erythroblastosis.

In a series of 49 patients given 100 intrauterine transfusions for erythroblastosis numerous obstetrical problems were encountered which were not directly related to the procedure. The purpose of this paper is to describe the difficulties experienced and to consider why these could have been anticipated.All of the mothers endured considerable emotional strain. Complications, which in previous pregnancies contributed to producing their Rh sensitization, tended to recur. Deliveries were carried out between 26 and 35 weeks' gestation, at which stage induction was difficult and labour imperfect. In 24 cases the fetus was alive at the onset of labour. The other 25 cases presented the problems of intrauterine death, nine of which occurred in the dangerous second trimester.Because of the coincidental obstetrical problems and the difficulties inherent in intrauterine fetal transfusion, these cases should be managed only in centres equipped to deal with all possible complications.

Adult↗

The treatment of erythroblastosis with promethazine hydrochloride.

Seventy-two patients with Rh erythroblastosis were treated with promethazine hydrochloride (P-HCl) during a seven-year period. Compared to the pregnancy outcome of the immediately preceding pregnancies, we have found a significant decrease in perinatal mortality and exchange transfusions. No significant toxicity from P-HCl treatment has been noted, and none of these patients developed preeclampsia.

Amniotic Fluid↗

Sensorineural outcome at 2 years for survivors of erythroblastosis treated with fetal intravascular transfusions.

OBJECTIVE: To determine the sensorineural outcome at 2 years of age in a complete cohort of survivors of fetal intravascular transfusions. METHODS: From March 1984 to May 1990, 38 of 52 consecutive fetuses (73%) suffering from severe erythroblastosis survived attempted intravascular transfusions at the Royal Women's Hospital, Melbourne. At 2 years of age, corrected for prematurity where appropriate, the survivors had a psychological assessment, including the mental developmental index of the Bayley scales, and a standardized neurodevelopmental examination. RESULTS: Only one transfused child had a severe sensorineural disability, with severe developmental delay and multiple minor motor seizures. Another child was moderately disabled with spastic hemiplegia. In neither case were complications of an intravascular transfusion the likely explanation for the disability. Only one other child had a mental developmental index in the suspect range. The remaining 35 children (92.1%) had no sensorineural disability. The overall rate of sensorineural impairments and disabilities was lower in the group transfused than in previous reports of survivors of intraperitoneal transfusions. The mean mental developmental index was significantly higher in the transfused group than in a control group of normal birth weight children. CONCLUSION: Children who survive fetal intravascular transfusions compare favorably not only with other high-risk survivors, but also with low-risk children.

Blood Transfusion, Intrauterine↗

[The development of children following intra-uterine transfusions in severe Rh-erythroblastosis (author's transl)].

The development of 18 children who had received 1--3 intra-uterine transfusions (IUT) because of severe Rh-erythroblatosis was followed over the first few years of life and finally checked when they were 2--6 years old. All of them were premature, 2 were born with hydrops, 1 with pre-hydrops. There were many other perinatal riskfactors (asphyxia, trouble with respiration, acidosis, severe anemia, hyperbilirubinemia). Examination (general and neurologic) was supplemented by EEG and psychologic testing )Kramer test, Vineland maturity scale, Denver development scales). No child showed signs of severe cerebral damage. 2 children had unequivocal pathologic signs (slight to medium spastic diplegia or hemipegia with corresponding focal findings in EEG). 3 further children showed minimal cerebral signs without disability. Development of intelligence was notably good throughout. Observations showed abnormal neurologi-signs more often during the first 2 years of life than later. Psychologic examinations, too, showed clear improvement with age. Results are satisfactory and confirm that IUT as a prenatal treatment with very severe Rh-Erythroblastosis is justified.

Age Factors↗

Treatment of obstructive jaundice in erythroblastosis fetalis with ursodeoxycholic acid (UDCA): a case report.

OBJECTIVE: To report a significant improvement of direct hyperbilirubinemia values, in an infant with cholestasis secondary to erythroblastosis fetalis, after treatment with ursodeoxycholic acid (UDCA). STUDY DESIGN: Case report. RESULTS: A full term infant, with total and direct bilirubin values of 26 mg/dl (445 micromol/l) and 24.5 mg/dl (419 micromol/l), respectively, on the third day of life, had total and direct bilirubin values of 8.2 mg/dl (140 micromol/l) and 6.9 mg/dl (118 micromol/l), respectively, after 2 days of treatment with UDCA. Because the natural course of this cholestasis takes several weeks to resolve, the observed improvement is highly suggestive of a direct effect of UDCA on the disease course. CONCLUSION: This treatment may add a new therapeutic option to the limited measures available for this condition, although further studies regarding safety and its mechanism of action are needed before it can be routinely recommended.

Cholagogues and Choleretics↗

Increased expression of avian erythroblastosis virus E26 oncogene homolog 1 in World Health Organization grade 1 meningiomas is associated with an elevated risk of recurrence and is correlated with the expression of its target genes matrix metalloproteinase-2 and MMP-9.

BACKGROUND: The transcription factor avian erythroblastosis virus E26 (V-Ets) oncogene homolog 1 (Ets-1) is involved in tumor development and progression through the transcriptional regulation of several matrix-degrading enzyme systems, including matrix metalloproteinases (MMPs). It has been demonstrated that the MMPs are expressed strongly in high-grade meningiomas. To determine the biologic significance of Ets-1 in the progression of benign meningiomas, the authors investigated the expressions of Ets-1 and its target genes MMP-2 and MMP-9 in primary and recurrent, Grade 1 meningiomas. METHODS: The expression levels of Ets-1, MMP-2, and MMP-9 were examined by immunohistochemistry in 70 Grade 1 meningiomas, including 36 primary tumors without recurrence after 5 years of follow-up and 17 pairs of primary tumors and subsequent recurrences. RESULTS: The results demonstrated higher expression of Ets-1, MMP-2, and MMP-9 proteins in meningiomas with subsequent recurrences compared with meningiomas from patients who had no recurrences (P < .001). In addition, Ets-1 expression was correlated with the expression of both MMP-2 and MMP-9. CONCLUSIONS: Ets-1 may be involved in meningioma recurrence by up-regulating MMP-2 and MMP-9. Increased expression of these genes in World Health Organization grade 1 meningiomas may serve as an indicator for a high risk of recurrence.

Aged↗

v-erbB oncogene expression accounts for most variations in protein synthesis after avian erythroblastosis virus infection of chicken embryo fibroblasts: a two-dimensional electrophoresis study.

The effect of the v-erbA and/or v-erbB oncogenes on cellular gene expression was investigated after separation by two-dimensional polyacrylamide gel electrophoresis of [35S]methionine-labelled proteins from chicken embryo fibroblasts (CEF), infected by either the avian erythroblastosis virus (AEV) carrying both oncogenes, or by viruses carrying only one of them. We observed significant changes in the synthesis of 34 proteins in AEV-transformed CEF as compared with control cells. The synthesis of 24 of them was increased while the synthesis of the other 10 proteins was decreased. The expression of v-erbB alone is necessary and sufficient to induce changes in the synthesis of 27 proteins while the 7 remaining modifications are observed only in cells expressing v-erbB together with v-erbA. Moreover, the deregulation of protein synthesis by v-erbB-expressing viruses was correlated with the morphological transformation state of cells.

Alpharetrovirus↗

Molecular cloning and characterization of the chicken DNA locus related to the oncogene erbB of avian erythroblastosis virus.

Chicken cell DNA contains sequences which are homologous to the avian erythroblastosis virus oncogene v-erb. These cellular sequences (c-erb) have been isolated from a library of chicken cell DNA fragments generated by partial digestion with AluI and HaeIII and shown to be shared by at least two loci in the chicken DNA. One of them, denoted c-erbB, contains approximately 1.8 kilobase pairs of chicken DNA homologous to the 3' part of the v-erb oncogene (v-erbB). Restriction mapping studies show that the c-erbB DNA sequences homologous to v-erbB are distributed among six EcoRI fragments located in a single genomic region. Heteroduplexes between v-erbB in viral RNA and cloned c-erbB DNA show that the chicken DNA sequences homologous to v-erbB are interrupted by 11 DNA sequences not present in the v-erb oncogene. We conclude from our data that the c-erbB locus might represent the cellular progenitor for the v-erbB domain of the v-erb oncogene.

Alpharetrovirus↗

Isolation and characterization of multiple human genes homologous to the oncogenes of avian erythroblastosis virus.

Human DNA sequences complementary to the oncogenes v-erbA and v-erbB of avian erythroblastosis virus have been isolated from a genomic DNA library. Two clones, lambda he-A1 and lambda he-A2, were related to the erbA gene and one to the erbB gene (lambda he-B). The two erbA genes were only distantly related to each other as judged from hybridization analysis. Furthermore, human chromosomal DNA appears to contain one or two additional genes analogous to the lambda he-A2 sequence, whereas the mouse genome contained only two genes complementary to lambda he-A1 and lambda he-A2, respectively. Polyadenylated RNA species, 5.0 kb in size, were found in the human HeLa and the human hematopoietic K562 cell lines, suggesting that at least some of the erb-related genes are active and do not represent pseudogenes. Taken together, the data demonstrate that two distantly related classes of erbA genes exist in human and mouse DNA, and that multiple copies of genes belonging to one of these two classes exist in the human genome.

Alpharetrovirus↗

Altered globin gene transcription pattern and the presence of a 7-8 kb alpha A globin gene transcript in avian erythroblastosis virus-transformed cells.

Immature chick erythroid cells transformed by avian erythroblastosis virus (AEV) display an altered pattern of globin gene transcription leading to the abortive phenotypic expression of such transcripts. Detectable adult globin gene-specific RNA sequences, confined exclusively to the nucleus, are uniquely of the alpha A type. The alpha A globin-specific sequences occur in transcripts 7-8 kb long from which the 5' contiguous alpha D gene product is absent, and also in fragments smaller than 9S globin mRNA. The implication of this observation for schemes of post-transcriptional regulation of gene expression and viral transformation are discussed.

Alpharetrovirus↗

A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes.

We have characterized the v-erbA and v-erbB oncogenes of td359, a transformation-defective mutant of avian erythroblastosis virus (AEV) unable to transform erythroblasts, and the revertant r12, obtained after in vivo passage of the mutant. Molecular cloning, sequencing, construction of chimeric viruses and testing of their oncogenic capacities revealed that both oncogenes of td359 are mutated and biologically defective. The r12 virus, although still containing a mutant v-erbB gene, recovered its erythroid transforming potential by acquiring a highly active gag-erbA gene. These results demonstrate that two co-operating oncogenes, an active v-erbA and a defective v-erbB, can transform a cell type not transformed by either oncogene alone. Furthermore, a single amino acid substitution inactivated the td359 v-erbA protein and we show that its reversion led to the reactivation of the protein. This lesion is located in the same region as several previously described inactivating mutations of glucocorticoid receptors, suggesting that the structure/function relationship of the virally transduced form of the c-erbA/thyroid hormone receptor is closely similar to that of steroid hormone receptors.

Alpharetrovirus↗

Erythroblast cell lines transformed by a temperature-sensitive mutant of avian erythroblastosis virus: a model system to study erythroid differentiation in vitro.

A continuous chicken erythroblast cell line transformed by the temperature-sensitive mutant ts34 of avian erythroblastosis virus was developed. This cell line, designated HD3, could be induced to terminally differentiate by shift to the nonpermissive temperature. The differentiated cells resembled erythrocytes as judged by morphology, expression of hemoglobin as determined by benzidine staining and radioimmunoassay, and by the expression of differentiation-specific cell surface antigens. Terminal differentiation was dependent on an erythropoietin-like activity present in anemic chicken serum. In contrast, induction of differentiation in the same cells by butyric acid was erythropoietin independent and did not lead to the formation of erythrocytes. In addition, we found that the responsiveness to temperature inducibility and to butyric acid could be dissociated in variant sublines of HD3 and that both types of differentiation inducers appear to act via different pathways.

Alpharetrovirus↗

Immunoblotting with polyclonal and monoclonal antibody to avian myeloblastosis protein p27: studies of liver proteins in chickens with erythroblastosis.

An antigen detected by complement fixation with polyclonal antibody to avian myeloblastosis virus (AMV) antigen p27, appears in the livers of chickens inoculated with avian erythroblastosis virus (AEV). It can be demonstrated at the 30,000 dalton (30K) molecular weight level by Western immunoblotting of electropherograms of AEV infected liver extracts. The 30K protein reacted strongly with this polyclonal antibody but only weakly with a monoclonal antibody to the same viral antigen and possible explanations for this have been suggested. Both antibodies also appeared to react with other than viral components in the preparations of AMV used. As this apparent non-specific attachment of highly specific antibody may have as its explanation the failure of the gelatin to prevent nonimmunologically determined binding of the immunoglobulin; other blocking agents should be investigated.

Alpharetrovirus↗

[Cold agglutinin disease--initial description in erythroblastosis and polycythemia vera].

The cold agglutinin disease is a hemolytic anemia induced by antibodies. Beside other etiological factors the disease is associated with tumors. In this paper cold agglutinin disease combined with erythroblastosis and combined with polycythemia vera is presented at the first time. In one case malignant proliferation followed the appearance of cold agglutinin antibodies. Blood transfusion, plasmapheresis, corticosteroids and chlorambucil were not successful. In the other case antibodies were temporarily expressed after a long time of malignant proliferation. Blood transfusion and corticoids were sufficient. Production of antibodies as a kind of tumor defence is discussed as reason for hemolysis. "Cross reacting antigenity" between normal and malignant erythrocytes is postulated.

Aged↗

Expression of differentiation and age-related antigens on chicken erythroleukemia cells transformed by avian erythroblastosis virus (AEV).

Immature circulating chicken red cells express on their surface two antigenic molecules referred to as Im 48 kD and Im 140 kD antigens. The Im 140 kD antigen is not present beyond the erythroblast stage while the expression of Im 48 kD antigenic molecule remains detectable on circulating erythrocytes of embryos and young chickens, but not on erythrocytes of adult animals. In addition to Im 48 kD and Im 140 kD antigens, the avian erythroblastosis virus (AEV)-transformed erythroid cells express two novel high molecular weight (MW) immature antigens referred to as Im 150 kD and Im 160 kD. Since the transformed erythroid cells are apparently blocked at a stage close to the colony-forming units erythrocytic (CFU-E), these molecules might be expressed on these progenitor cells. The age-related antigenic molecules referred to as E1 48 kD and A 40 kD/A 85 kD antigens are detected on erythrocytes of embryos (and young chickens) and adult animals respectively. The E1 48 kD antigen as well as an antigen related to the A 40 kD were also detected on AEV-transformed erythroid cells deriving from both young chicken bone marrow and yolk sac. The presence of an adult antigen on the embryonic cells might well be related to the transformation by AEV, since the yolk sac CFU-E progenitor cells do not bear the adult antigenicity.

Alpharetrovirus↗

Morphological transformation, autonomous proliferation and colony formation by chicken heart mesenchymal cells infected with avian sarcoma, erythroblastosis and myelocytomatosis viruses.

Normal chicken heart mesenchymal cells at low density in monolayer culture in plasma-containing medium have a polygonal shape and are proliferatively quiescent. The combination of epidermal growth factor and insulin at hyperphysiological concentration, an insulin-like growth factor surrogate, causes these cells to assume a fusiform shape and to increase 40-fold in number during four days of incubation. These mitogenic hormones do not, however, induce normal chicken heart mesenchymal cells to form colonies in agarose suspension culture. Chicken heart mesenchymal cells infected with the Schmidt-Ruppin or Prague-A strains of Rous sarcoma virus or with the Fujinami or Y73 avian sarcoma viruses assume spindle and round shapes, increase 50-100 fold in number during four days of monolayer culture in the absence of mitogenic hormones and form macroscopic colonies during 3-4 days of agarose suspension culture. The autonomous (mitogenic hormone-independent) proliferation, in monolayer culture, of cells infected with temperature-sensitive transformation mutants of Rous sarcoma virus (tsNY68, tsNY72, tsLA24, tsLA29) is temperature-sensitive. Chicken heart mesenchymal cells infected with avian erythroblastosis virus assume spindle shapes and proliferate in monolayer culture at a rate comparable to that of sarcoma virus-infected cells but do not, however, form colonies in agarose suspension culture. Cells infected with the myelocytomatosis virus MC29 assume stellate shapes and increase 18-fold in number during four days of monolayer culture. Cells infected with the myelocytomatosis virus MH2 assume fusiform shapes and increase fourfold in number during four days of monolayer culture. Neither MC29 nor MH2 renders chicken heart mesenchymal cells capable of colony formation in agarose suspension culture. Infection with avian leukosis viruses (RAV-1, RAV-2, RPL-42) or with transformation-defective mutants of Rous sarcoma virus (tdNY105, 107, 109) does not affect the morphology or proliferative behavior of chicken heart mesenchymal cells. Monolayer culture of chicken heart mesenchymal cells in plasma-containing medium appears, therefore, to define the ability of onc genes of acute transforming avian retroviruses to induce autonomous (mitogenic hormone-independent) cell proliferation, the essential characteristic of neoplasia. The differences in transformed morphology and rates of autonomous proliferation between cells infected with different acute transforming retroviruses probably reflects differences in the modes of action of the transforming proteins encoded by the onc genes of the respective viruses.(ABSTRACT TRUNCATED AT 400 WORDS)

Alpharetrovirus↗