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E Kleihauer

Publications and source records attributed to E Kleihauer.

At least 37 records · Page 2Linked to original sources
PubMed1988

[The molecular basis of hereditary persistence of fetal hemoglobin (HPFH). Clinical importance of the hemoglobin switching mechanism with special reference to Corfu delta beta zero thalassemia].

The haemoglobinopathies are a group of autosomal recessively inherited diseases that are common among populations in the Mediterranean, in Africa and large parts of Asia. In Germany, the immigration of people from those parts of the world has resulted in an increased occurrence in particular of beta thalassaemia. Homozygous patients usually become transfusion dependent during the first year of life as the excess of alpha globin chains in the erythroid precursors causes a most severe dyserythropoietic anaemia. Genetic determinants that diminish the alpha globin chain excess are thus clinically significant. Here, we describe the molecular genetic changes that result in an increased gamma globin gene expression and hende in a binding of alpha globin chains as HbF. We discuss the significance of those changes for the clinical course of beta thalassaemia and for the elucidation of the ontogenetic processes of gene regulation during the perinatal haemoglobin switch.

DNA↗
PubMed1988

[Diagnosis and treatment of aplastic anemia].

Severe aplastic anemia is a rare disorder in childhood. Among various therapeutical strategies bone marrow transplantation (BMT) and immunosuppressive treatment with antithymocyte globulin (ATG) have proven to be most successful. Priority should be given to BMT over ATG treatment for patients with HLA-identical donors. Patients with Fanconi's anemia require a reduced conditioning program with cyclophosphamide and irradiation for BMT. Own experiences indicate that cooperative studies are highly needed to improve medical care for patients with severe aplastic anemia.

Anemia, Aplastic↗
PubMed1987

[Treatment of Fanconi anemia by bone marrow transplantation].

We report on our experience with allogenic bone marrow transplantation in the treatment of Fanconi anemia. Eight patients were treated, ranging in age from 5 to 17 years. Beside severe hemopoietic insufficiency, all patients exhibited typical cytogenetic abnormalities with an increased rate of chromosomal breaks, while constitutional signs of the disorder were rather variable. Marrow donors were HLA-identical siblings. For conditioning, we used cyclophosphamide at 5 mg/kg on 4 consecutive days followed by thoraco-abdominal irradiation at 5 Gy with full lung shielding. For prophylaxis of graft versus host disease, cyclosporin A was given except in 3 cases who received T-cell depleted marrow. In 2 of the latter cases, graft failure was observed, successfully reversed in one by retransplantation. All others showed prompt and stable engraftment of donor cells. Complications of graft versus host disease developed in 2, requiring prolonged immunosuppressive treatment. Of 8 transplanted patients, 7 survive. With the exception of a recently treated girl, they have normal stable marrow functions. Our results confirm that successful treatment of Fanconi anemia is possible in a majority of patients with HLA-identical donors.

Adolescent↗
PubMed1986

Additional c-abl/bcr rearrangements in a CML patient exhibiting two ph1 chromosomes during blast crisis.

Recent data suggest that two human genes, c-abl on chromosome 9 and bcr on chromosome 22, are involved in the generation of Ph1-positive CML. To examine a possible role of these sequences in transition from chronic towards blastic phase, rearrangements within bcr were analysed in 4 patients with Ph1-positive CML during chronic and acute phase. In 3 patients bcr rearrangements were identical in both phases, while in a fourth patient with duplicated Ph1 an amplified additional bcr fragment was detected in acute phase. Northern blot analysis of blast cells of the latter patient showed a novel 10.3 kb RNA species that replaced the altered 8 kb RNA transcript usually found in Ph1-positive CML.

Adolescent↗
PubMed1986

Conversion of acute undifferentiated leukemia phenotypes: analysis of clonal development.

The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of beta-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and confirm the value of Ig gene analysis as marker for cellular clonality.

Adult↗
PubMed1986

Acute undifferentiated leukemia: implications for cellular origin and clonality suggested by analysis of surface markers and immunoglobulin gene rearrangement.

Although B cell leukemias and, recently, T cell leukemias can be identified both by surface marker and molecular analysis, there remains a population of acute undifferentiated leukemias (AUL) that cannot be allocated definitively to a single cell lineage. AUL was diagnosed in nine patients according to stringent criteria. We combined both immunologic and molecular approaches to analyze further the ambiguous origin of AUL cells. Southern blot analysis revealed rearranged Ig heavy-chain genes in seven patients and indicated a biclonal or oligoclonal leukemic cell population in three of them, including one case of AUL with translocation (4;11). Analysis of cell surface markers showed expression of at least one early B cell-associated antigen (BA-1, BA-2, B4, UL-38) in six of these seven patients, with coexpression of a myeloid antigen (VIM-2) in three patients. Leukemic cells of two other patients neither exhibited Ig chain gene rearrangements nor expressed B cell-associated antigens. T cell receptor beta-chain genes showed germline configuration in all nine cases. Our results demonstrate heterogeneity among AUL patients based on molecular and surface marker analyses and suggest that most AUL blast cells are derived from a precursor cell that shares phenotypic and genotypic characteristics of early B cells with certain surface antigens of myeloid cells, in some cases of AUL more than one abnormal cell clone or subclone may exist, and the cellular origin, at least of some AULs exhibiting t(4;11), may be truly B cell lineage committed.

Antibodies, Monoclonal↗
PubMed1986

bcr rearrangement and translocation of the c-abl oncogene in Philadelphia positive acute lymphoblastic leukemia.

The Philadelphia (Ph1) chromosome, the cytogenetic hallmark of chronic myeloid leukemia (CML), has also been detected in a significant number of acute lymphoblastic leukemias (ALL). Using in situ hybridization, we demonstrate that in accordance with observations in CML the Ph1 chromosome in ALL patients is the result of a consistent translocation of the c-abl oncogene to the Ph1 chromosome. Southern blot analysis using bcr probes, however, suggests that Ph1-positive ALL includes heterogeneous leukemic subtypes: six ALL patients showed bcr rearrangements as observed in CML; in three other patients recombination involving 5' bcr sequences could be demonstrated, but the corresponding translocated 3' bcr sequences were not detectable. A third group of five patients did not show any bcr rearrangements at all. Northern blot analysis using RNA from three Ph1-positive ALL patients revealed that in the leukemic cells of two patients larger c-abl mRNA transcripts were present, as in CML. In the RNA of one patient without a detectable bcr rearrangement, only the normal c-abl mRNA transcripts are present. The observed heterogeneity in bcr rearrangements of this group of Ph1-positive ALL patients is in contrast with the consistent results obtained in more than 50 Ph1-positive CML patients investigated in chronic and acute states.

Chromosome Deletion↗
PubMed1985

C-abl and bcr are rearranged in a Ph1-negative CML patient.

Chromosomal analysis of a patient with chronic myelocytic leukemia (CML) revealed a translocation (9;12) (q34;q21) without a detectable Philadelphia chromosome (Ph1). Using molecular approaches we demonstrate (i) a rearrangement within the CML breakpoint cluster region (bcr) on chromosome 22, and (ii) a joint translocation of bcr and c-abl oncogene sequences to the derivative chromosome 12. These observations support the view that sequences residing on both chromosome 9 (c-abl) and 22 (bcr) are involved in the generation of CML and suggest that a subset of Ph1-negative patients may in fact belong to the clinical entity of Ph1-positive CML.

Adult↗
PubMed1985

Ultrasound characteristics of the pancreas in children with cystic fibrosis.

Eighteen patients (3 months to 16 years) with cystic fibrosis (CF) were examined with a real-time mechanical sector-scanner (5 MH transducer). Compared with age-matched controls, each CF patient showed morphologic changes in the pancreas on abdominal ultrasound examination. A very common finding was a decrease in organ anterior-posterior diameters (CF versus controls: head, 1.25 +/- 0.38 cm versus 2.44 +/- 0.39 cm; body, 0.56 +/- 0.35 cm versus 0.98 +/- 0.3 cm; tail, 0.83 +/- 0.28 cm versus 1.81 +/- 0.38 cm) and a pronounced, age-independent increase in tissue echogenicity. In younger patients, small cystic degenerations could be observed in the pancreatic tail. No correlation could be found between ultrasound morphology, especially pancreatic duct imaging, and exocrine pancreatic function.

Adolescent↗
PubMed1985

Cor triatriatum masked by primary pulmonary hypertension.

In a 17-month-old boy with clinical signs of right heart failure, the diagnosis of primary pulmonary hypertension was made, based on cardiac catheterization findings with high pulmonary arterial pressure and normal pulmonary wedge pressure although two-dimensional echocardiography demonstrated a left atrial membrane. Postmortem examination confirmed a left atrial membrane (cor triatriatum), and the microscopic examination revealed the histological pattern of primary pulmonary hypertension. Due to reduced pulmonary blood flow, pulmonary venous obstruction was masked and could not be assessed by measuring pulmonary wedge pressure.

Diagnosis, Differential↗
PubMed1985

Involvement of chromosome 9 in variant Ph1 translocation.

Cytogenetic analysis of a patient with chronic myelocytic leukemia revealed a translocation (21; 22) (q 22; q 11) without a detectable involvement of chromosome 9. By in-situ hybridization studies, however, we demonstrate a reciprocal translocation of sequences from chromosome 9 (c-abl) to Ph1 and chromosome 22 (bcr) to 9, respectively. These observations suggest a consistent participation of chromosome 9 in the Ph1 translocation, regardless of the cytogenetic subtype.

Chromosomes, Human, 6-12 and X↗
PubMed1985

[Cytomegalovirus hyperimmune globulin prophylaxis in bone marrow transplants in children with various diseases].

The effect of hyperimmune globulin for the prevention of cytomegalovirus (CMV) infections following bone marrow transplantation (BMT) was evaluated in 21 children with various diseases and compared to a historical group of 23 children without prophylaxis. A higher incidence of interstitial pneumonia (19%) as well as CMV-associated infections with or without pneumonitis (29%) could be demonstrated in patients with CMV-prophylaxis as against the rate of interstitial pneumonia (4%) and CMV-infections (8%) in children without prophylaxis. This surprising observation was very likely due to selection of patients with high risk features and higher incidence of GVHD in the prophylaxis group. The analysis of patients with prophylaxis failure shows a low CMV-infection rate in initially seronegative marrow recipients and a high risk for CMV-infections in seropositive patients. Therefore, even though CMV-infections could not be completely abrogated, hyperimmune globulin administration might have reduced CMV-complications in seronegative patients. In CMV-seropositive marrow recipients, however, this type of prophylaxis remains unsatisfactory in preventing severe CMV-infections caused by virus reactivation.

Adolescent↗
PubMed1984

Immunoreconstitution in severe combined immunodeficiency after transplantation of HLA-haploidentical, T-cell-depleted bone marrow.

Immunological reconstitution by transplantation of HLA-haploidentical, paternal bone marrow was attempted in four infants with severe combined immunodeficiency who lacked HLA-identical donors. To prevent graft-versus-host disease, T lymphocytes were removed from the grafts by agglutination with soybean agglutinin and rosette formation with sheep red blood cells. None of the patients received conditioning treatment before transplantation. Normal, donor-derived cellular immune functions developed in all four patients within several months of transplantation. Threatening complications of graft-versus-host reactions were not seen. All four patients remain in excellent health 12-15 months after discharge home, with persisting normal T-cell functions.

Bone Marrow↗
PubMed1984

Hemoglobin Köln: analysis of linkage relationships between the mutant gene and polymorphic restriction sites in the beta-globin gene cluster.

Nuclear DNA has been analyzed by means of restriction endonuclease mapping procedure to identify chromosomes that carry mutant Hb Köln beta-globin genes in a family with individuals heterozygous for this disease. Inherited DNA polymorphisms within the beta-globin gene cluster yielded a direct linkage of the Hb Köln mutation to haplotype constellations that are diagnostic for further offspring.

Carrier Proteins↗
PubMed1984

The place of intravenous immunoglobulin (IgG i.v.) therapy in thrombocytopenia.

Acute ITP following infection in children has a high rate of spontaneous remission. Since the platelet count is not uncommonly profoundly depressed, ITP is associated with a mortality of around 1%. The aim of treatment in ITP is to prevent bleeding. As a rule, this can only be achieved by normalizing the platelet count. Intravenous immunoglobulin offers certain advantages over conventional steroid therapy. Moreover, two out of three patients with chronic ITP respond to IgG i.v. The characteristic features of ITP in pregnancy, thrombocytopenia in babies born to mother with ITP and neonatal isoimmune thrombocytopenia are discussed.

Adrenal Cortex Hormones↗