PubMed Health⌕ Search

Biomedical subjects

E Signer

Publications and source records attributed to E Signer.

At least 37 records · Page 2Linked to original sources
PubMed1987

Glycine-cysteine substitution at codon 13 of the N-ras proto-oncogene in a human T cell non-Hodgkin's lymphoma.

Tumor-derived DNA from a non-Hodgkin's (T cell) lymphoma patient, assayed by NIH3T3 transfection followed by inoculation of cells into nude mice, was found to contain an activated N-ras proto-oncogene. The mode of activation was determined by hybridization with N-ras-specific oligonucleotide probes detecting mutations at codons 12, 13 and 61. A transversion in codon 13 (GGT----TGT) resulting in replacement of glycine13 by cysteine13 in ras p21 protein was found. The mutation was detected in DNA from mouse tumors induced by transfected NIH3T3 cells and in DNA from patient tumor lymphoblasts. The patient was heterozygous for this mutation. These data identify the first base of codon 13 as a novel mutation site in ras genes and indicate that cysteine at position 13 of the ras p21 is a transforming substitution.

Cell Transformation, Neoplastic↗
PubMed1986

Reactivity of monoclonal antibodies LAU-A1 and anti-Y 29/55 in T and B cell malignancies of children: correlation with immunological markers and clinical data.

The monoclonal anti-pan-T cell antibody LAU-A1 stained neoplastic T cells arrested at different levels of maturation from all 21 children with T cell malignancies examined. Particularly in 7 patients with immature T cell neoplasia staining for LAU-A1 facilitated the recognition of a T cell origin of the malignant cells. Only 40% of these immature T cell malignancies were associated with an anterior mediastinal mass. A subdivision of T cell neoplasia into 4 differentiation-related subgroups did not permit to make predictions regarding the patients' survival. Despite the rather uniform clinical presentation the immunological phenotypes of tumor cells in 14 children with B cell non-Hodgkin's lymphoma (B NHL) were heterogeneous. Tumor cells lacked surface immunoglobulins (2 patients), expressed IgM only (7 patients), IgM and IgD (3 patients) or IgM, IgD and IgA (2 patients). Regardless of surface immunoglobulin expression anti-Y 29/55 stained practically all recognizable tumor cells of all B NHL examined. No correlation was found between the number of heavy-chain isotypes expressed on tumor cells and the survival of the patients. The only long-term survivors were 3 children transplanted with autologous bone marrow which had been purged in vitro with anti-Y 29/55 and complement.

Adolescent↗
PubMed1986

Treatment of severe aplastic anemia.

A total of 100 patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983: 28 patients had an HLA-identical sibling donor and were treated with bone marrow transplantation, and 72 patients without an HLA-identical sibling donor were given antilymphocyte globulin followed by oral low-dose androgen therapy. At 1 1/2-9 years after treatment, 13 patients (46%) survive in the transplant group and 45 patients (75%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematologic complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hematopoiesis: macrocytosis, mild granulocytopenia, and mild thrombopenia. Relapse (11 of 72 patients) and clonal hematologic disorders, such as paroxysmal nocturnal hemoglobinuria (four patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. Despite this, we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long, sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplant or antilymphocyte globulin.

Adolescent↗
PubMed1985

[Invasive pulmonary aspergillosis--a diagnostic and therapeutic problem in patients with severe aplastic anemia].

Three young patients with severe aplastic anemia undergoing intensive immunosuppressive therapy developed fever and pulmonary infiltrates during longlasting severe granulocytopenia, despite multiple broad spectrum antibiotic combinations and granulocyte transfusions. Invasive pulmonary aspergillosis was diagnosed only by thoracotomy. In conjunction with high dose amphotericin-B therapy complete resolution of aspergillosis was achieved in two cases, paralleled by slow recovery of bone marrow function, whereas in the third case only a partial remission was possible together with transient amelioration of granulopoiesis. We suggest early aggressive surgical methods to establish the diagnosis of aspergillosis in these severely menaced patients, so that antifungal therapy with high dose amphotericin-B can be initiated at an early stage.

Adolescent↗
PubMed1985

Increased prevalence of minor anomalies in childhood malignancy.

Body measurements were taken and the prevalence of major malformations and of 57 minor anomalies was determined in 106 children with malignant disease, in 81 of their sibs, and in 106 control subjects matched to the patients according to sex, age and ethnic origin. Leukaemic children had a significantly smaller head circumference than the corresponding control children, but no significant differences in height, weight, anthropometric and syndromologic indices were found. No differences were observed in the frequency of associated major malformations including renal malformations detectable by sonography. The prevalence of minor anomalies was significantly higher in the patients with malignant disease and their sibs than in the control children: 69.2% of the patients, 63.0% of the sibs and 34.6% of the control subjects had at least one minor anomaly. When two and more minor anomalies were considered, the prevalence figures were 36.5%, 29.6% and 12.5%, respectively. Among the single minor anomalies only the Sydney line was significantly more frequent in patients with solid tumours. No specific association of an individual dysplasia or a pattern of minor anomalies with a given tumour could be established.

Adolescent↗
PubMed1984

Genetic analysis of familial erythrophagocytic lymphohistiocytosis.

A family with two patients suffering from familial erythrophagocytic lymphohistiocytosis (FEL) is described. Reports on FEL found in the literature were collected and the family trees reconstructed. Genetic analysis of this material indicated that FEL is an autosomal recessive hereditary disease. This conclusion is supported by the following evidence: considerably increased consanguinity rate; complete concordance in monozygotic twins; more frequent occurrence in inbred populations and in cousins; limitation of cases to one generation, and results of segregation analysis.

Consanguinity↗
PubMed1983

[Bone marrow transplantation in acute lymphatic leukemia during the first remission].

9 patients with acute lymphoblastic leukaemia (ALL) were transplanted in first remission. There were no leukaemic relapses and 6 patients became longterm survivors. Causes of death were GvHD in 2 and interstitial pneumonia in 1. 14 patients with ALL were grafted in later stages of the disease. 10 had a leukaemic relapse. One attained longlasting remission with chemotherapy, while 9 died. One patient died of CMV infection. Cotton wool lesions and haemorrhages in the retina posed a problem in patients with previous cranial irradiation. We recommend transplantation of ALL in first remission if a syngeneic or HLA-identical sibling is available, particularly if the patient has poor risk factors for chemotherapy. Prophylactic cranial irradiation should be replaced by intrathecal methotrexate and/or cytosin arabinoside in these patients.

Adolescent↗
PubMed1983

[Bone marrow transplants--quo vadis?].

Early bone marrow transplantation (BMT) in leukaemia has enormously improved the results. Leukaemic relapse is rare, as is transplant-related mortality from interstitial pneumonia and severe graft-versus-host disease (GvHD). In aplastic anaemia the most important development is that treatment with ALG offers a real alternative to BMT which is of crucial importance for all patients without a histo-compatible family donor. The main problems of BMT are the lack of histocompatible donors and GvHD. In leukaemia, relapse is still an additional problem. The new immunosuppressive agent cyclosporin-A (CyA) has made an important contribution to the prophylaxis of severe GvHD. In future the results with CyA are potentially improvable by combination with other immunosuppressive agents. It is important that the use of HLA-semicompatible family donors, unrelated donors or alternative stem cell sources should become feasible. The value of autologous BMT is difficult to judge because in most instances it has been performed in patients with endstage disease. In several congenital diseases there are alternatives to BMT, such as genetic engineering. Although many problems of BMT still have to be solved, this procedure has an important place in modern medicine.

Bone Marrow Transplantation↗
PubMed1983

[Bone marrow transplantation in leukemia and aplastic anemia].

In a review of allogeneic bone marrow transplantation (BMT) for leukemia the following points proved to be of crucial importance: (1) combination of cyclophosphamide (Cy) and total body irradiation (TBI) for conditioning, (2) early BMT for acute leukemia (AL) in first remission and for chronic granulocytic leukemia (CGL) in chronic phase, (3) prophylaxis of graft-versus-host disease (GvHD) with cyclosporin-A (CyA). 50 successive BMT for leukemia performed in Basel between July 1979 and September 1982 are analyzed. 7 of 13 acute myelogenous leukemias (AML) and 8 of 9 acute lymphatic leukemias (ALL) grafted in first remission, and 7 of 10 CGL, are alive without signs of leukemia and without chronic problems. Of the patients grafted for AL in second remission or later, 3 of 6 AML and 6 of 12 ALL are alive. Severe GvHD was seen in 5 of 43 BMT between HLD identical siblings, in three of them combined with interstitial pneumonia. Thus the incidence of these two serious complications of allogeneic BMT has been drastically reduced with CyA compared to our previous experience with prophylactic methotrexate (MTX). 4 grafts were performed between HLA-haploidentical siblings. 3 of the 4 patients developed fatal GvHD. This implies that in this histocompatibility setting CyA alone is not sufficient. No problems were encountered in 3 syngeneic BMT. 12 leukemic relapses were observed. Relapse never occurred in ALL in first remission and never in CGL. 4 recurrences were seen in AML in first remission. All other relapses were in patients with AL grafted in stages other than first remission. In 86 successive patients with severe aplastic anemia (SAA) the following important advances were made: (1) it was shown that the majority of patients have sufficient hemopoietic stem cells and that after treatment with antilymphocyte globulin (ALG) over 70% have long-lasting remissions, (2) the combined treatment with ALG and high dose prednisone increases the remission rates to 90% and in addition shortens the supportive care period significantly. These developments are of crucial importance for patients without an HLA-identical sibling, (3) success rates of marrow transplants between HLA-identical siblings could be increased from 36% with prophylactic MTX to 67% using CyA.

Anemia, Aplastic↗
PubMed1983

A reliable screening test for childhood celiac disease: fluorescent immunosorbent test for gliadin antibodies. A prospective multicenter study.

The diagnostic value of gliadin antibody determination using the fluorescent immunosorbent test was examined in a prospective multicenter study comprising 251 children with malabsorptive disorders. Antibodies to gliadin were found in all 72 patients (100%) with active celiac disease (29 children with celiac disease proved by challenge, 43 with probable celiac disease). All children up to the age of 7 years had antibodies in high titers. By contrast, 96 (84%) of 114 children with other malabsorptive disorders and a normal mucosa or with partial villous atrophy had no gliadin antibodies, 14 (12%) had a low titer, and only four (3.5%) showed moderate to high titers. Four children with gastrointestinal tract symptoms of cow milk intolerance and a flat mucosa also showed no antibodies. In 24 of 29 children (83%) with cystic fibrosis and six of seven children with Crohn disease (biopsies not performed in either group), no antibodies could be detected. The others had low or elevated titers. In 25 children with acute gastroenteritis (not biopsied) antibodies were not found at hospital admission nor six weeks later after reintroduction of gluten. The determination of antibodies to gliadin with the fluorescent immunosorbent test is a reliable screening test for childhood celiac disease. In our series there were no false negative results in children with untreated celiac disease. A positive gliadin antibody titer is not proof of celiac disease. In each child the diagnosis must be confirmed by small intestinal biopsy even if the gliadin antibody titer is high. The detection of high titers of cow milk antibodies in 27% of patients with celiac disease is of no value.

Adolescent↗
PubMed1983

Bone marrow graft versus ALG in patients with aplastic anaemia.

Eighty-six successive patients with severe aplastic anaemia were admitted to this hospital between January 1976 and October 1982. They were treated and evaluated in a prospective study according to one protocol. 26 patients with an HLA identical sibling underwent bone marrow transplantation. Overall survival calculated according to Kaplan and Meier in this group is 47%, 60 patients without an HLA identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haploidentical marrow. All these 60 patients received low dose androgens after the procedure. In this study the marrow infusion did not significantly improve the results and overall survival was 74% compared to 70% in patients receiving only antilymphocyte globulin and androgens. In a current pilot study combining ALG and high dose prednisone we were able to further increase remission rates. Between HLA-identical siblings we improved the results of marrow transplants significantly by the use of cyclosporin-A instead of methotrexate for prophylaxis against GvHD.

Adolescent↗
PubMed1982

[Marrow transplantation in leukemia-recent trends].

Due to progress in conventional chemotherapy 50-60% of children with acute leukemia can be cured today. Despite these good results, however, 40-50% eventually will relapse and die. Other therapeutic modalities are therefore needed. Transplantation of bone marrow from an HLA-identical sibling offers this possibility. Initiated a decade ago as last therapy for end stage disease patients marrow transplantation is a well tolerated therapy today with well defined risks. In adults, marrow transplantation is clearly superior to conventional chemotherapy if performed early. The incidence of severe Graft-versus-Host-Disease, the major complication of marrow transplantation is much less after early transplantation and Cyclosporin-A, a new immunosuppressive agent further reduces severity of Graft-versus-Host-Disease. Since all complications are less in younger patients marrow transplantation is the therapy of choice for a child with leukemia having an HLA-identical sibling donor.

Acute Disease↗
PubMed1979

Antibodies to gliadin as a screening test for coeliac disease. A prospective study.

The diagnostic value of gliadin antibody determination using the fluorescent immunosorbent test was examined in a prospective study of 57 children with gastrointestinal disease. Antibodies to gliadin were found in all 20 patients with active coeliac disease, whereas 7 of these children (37%) had a normal xylose absorption test despite a flat small gut mucosa. Only 4 (14%) of 28 children with other gastrointestinal conditions had antibodies to gliadin, invariably in low titre. After at least 2 years on a gluten-free diet none of 9 children with coeliac disease in remission had demonstrable gliadin antibodies. The gliadin antibodies disappear slowly, within 6 to 24 months, after withdrawal of gliadin from the diet. 0.8% (5/606) of a healthy control group of children, adolescents and adults (not biopsied) had gliadin antibodies in low titre. Increased mean cow's milk antibody titres were demonstrable in 8 (40%) of 20 patients with active coeliac disease as well as in 9 (32%) of 28 patients with other gastrointestinal lesions. Our studies show that determination of circulating gliadin antibodies is a worthwhile screening test in suspected cases of coeliac disease. In patients so selected there is a definite indication for small intestinal biopsy to confirm the diagnosis.

Adolescent↗