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E Signer

Publications and source records attributed to E Signer.

At least 19 recordsLinked to original sources
PubMed2000

Increased withdrawal volume per deposit for pre-operative autologous blood donation in adolescents.

OBJECTIVES: This study was undertaken to assess the feasibility, tolerance, haemodynamic and haematologic effects of an aggressive phlebotomy schedule for autologous blood donation (ABD) in adolescents undergoing major orthopaedic surgery. METHODS: Twenty adolescents were studied prospectively; 10 patients in group A donated 20% of the circulating blood volume on 2 occasions, whereas 10 patients in group B donated 10% on 4 occasions. RESULTS: The amount of blood donated, subjective tolerance, cardiovascular changes during the procedure and pre-operative haemoglobin level did not differ between the study groups (group A 111+/-16 vs. group B 106+/-10 g/l). The increase in erythropoietin was greater and occurred sooner in group A than in group B. CONCLUSION: In adolescents ABD is feasible with a reduced number of appointments as they demonstrate tolerance to phlebotomies with a volume which is double the standard per deposit.

Adolescent↗
PubMed1999

Human minisatellites, repeat DNA instability and meiotic recombination.

Minisatellites include some of the most variable loci in the human genome and are superb for dissecting processes of tandem repeat DNA instability. Single DNA molecule analysis has revealed different mutation processes operating in the soma and germline. Low-level somatic instability results in simple intra-allelic rearrangements. In contrast, high frequency germline instability involves complex gene conversions and is therefore recombinational in nature, almost certainly occurring at meiosis. To determine whether true meiotic crossovers occur at human minisatellites, we have used polymorphisms near the repeat array to recover recombinant DNA molecules directly from sperm DNA. Analysis of minisatellite MS32 has revealed an intense and highly localised meiotic crossover hotspot centred upstream of the array, the first example of a human hotspot defined at the molecular level. This hotspot extends into the beginning of the repeat array, resulting in unequal and equal crossovers. Array crossovers occur much less frequently than array conversions but appear to arise by a common process, most likely by alternative processing of a recombination initiation complex. The location of MS32 at the boundary of a recombination hotspot suggests that this locus has evolved as a by-product of localised meiotic recombination activity, and that minisatellites might in general mark recombinationally proficient hotspots or hot domains in the genome. Finally, sperm crossover analysis makes it possible to explore the molecular rules that govern human meiotic recombination, and to detect phenomena such as meiotic drive that could provide a possible connection between recombination and DNA sequence diversity itself.

DNA↗
PubMed1998

The chicken CP49 gene contains an extra exon compared to the human CP49 gene which identifies an important step in the evolution of the eye lens intermediate filament proteins.

The gene structure for chicken CP49 gene is presented. It differs from the human CP49 gene with the presence of an extra exon in helix IB and the apparent loss of an intron, intron H. The CP49 gene localises to chromosome 2 in the chicken genome where it is flanked by homologues that map to human chromosome 10p13 (VIM) 6p24-p23 (BMP6). Two transcripts, CP49 and CP49ins, are produced from the single chicken CP49 gene. The difference is a 49-amino-acid insertion in helix IB of CP49 that is encoded by a novel exon found in the chicken CP49 gene. An extended helix IB is believed to be a characteristic of the ancestral intermediate filament protein as it is found in many invertebrate intermediate filament proteins but has been lost from all vertebrate intermediate filament proteins except the nuclear lamins. Although the intron position and length of the helix IB insert sequences in CP49ins differ to those found both in the invertebrate intermediate filament proteins and the vertebrate lamins, the CP49 gene is the first vertebrate cytoplasmic intermediate filament protein to be described with an extended helix IB. The chicken CP49 gene is also the first where differential splicing can remove such a feature. Human and bovine CP49 appear to have lost the helix IB insert sequences, and so the avian CP49 gene provides an interesting evolutionary link between the eye lens proteins and the ancestral intermediate filament protein.

Amino Acid Sequence↗
PubMed1998

Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia.

In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n = 25) or relapse (n = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13d; P = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 +/- 8% at 10 years. The probability of developing a late clonal disorder was 53 +/- 10% after multiple, as compared to 34 +/- 7% after single exposure (P = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

Adolescent↗
PubMed1997

Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation.

We observed the occurrence of celiac disease following allogeneic bone marrow transplantation in a patient transplanted for acute leukemia. The marrow donor was his HLA-identical sister, who had suffered from celiac disease since birth. The post-transplant period was characterized by recurrent episodes of diarrhea. Detailed workup showed atrophic intestinal mucosa on histology and anti-gliadin and anti-endomysium antibodies in the serum, features that were not present before transplantation. GVHD was absent at that time. The patient remains free of symptoms on gluten-free diet and slight immunosuppression. This case suggests transmission of celiac disease by bone marrow transplantation and supports the T cell concept in celiac disease.

Acute Disease↗
PubMed1996

[Autologous transplantation of hematopoietic precursor cells following CD34 selection].

Peripheral blood is increasingly used instead of bone marrow as a source of hemopoietic precursor cells for transplantation. The optimal technique still needs to be defined. Selection of CD34+ cells in transplant material may be of benefit in allogeneic and autologous peripheral blood precursor cell transplantation (PBPCT), since it allows elimination of unwanted CD34-negative cells, such as T-cells and contaminating tumor cells. We have evaluated the feasibility of CD34 selection in PB transplants and studied hemopoietic reconstitution after autologous transplantation of CD34 selected precursor cells. Between August 1994 and June 1995 CD34 selection was performed on 12 transplants for 9 patients with malignant disease (non-Hodgkin lymphoma [n = 5]; Ewing sarcoma [n = 1]; chronic lymphocytic leukemia [n = 1]; breast cancer [n = 1]; multiple myeloma [n = 1]). PBPC were collected with a Fenwall CS 3000 harvester after stimulation with G-CSF. For selection of CD34+ cells the Ceprate LC34 system (CellPro) was used. A median CD34 purity of 73% (range 40-94%) was achieved. The median number of CD34 positive cells per transplant was 4.8 x 10(6)/kg body weight (range 0.7-15.8). The median number of colony forming cells per transplant was 31 x 10(4)/kg body weight (range 1.5-131.3). For autologous PBPCT the minimal number of CD34 positive cells required in the transplantate was arbitrarily set at 1.0 x 10(6)/kg body weight. This number was achieved in 10 of the 12 transplants. The median loss of CD34+ cells during selection was 1.5 x 10(6)/kg body weight (range 0.2-6.4). In 2 patients the total number was reduced to below the critical value of 1.0 x 10(6)/kg. 7 of the 9 patients received the CD34 selected transplant after intensive chemotherapy and irradiation. The median follow-up time after PBPCT was 196 days (range 62-278). All 7 patients are now alive and with normal hemopoietic function. A granulocyte count above 0.5 x 10(9)/l and a platelet count above 20 x 10(9)/l was achieved on day 14 (median), and on day 19 after PBPCT. We conclude that CD34 selection is technically feasible and that CD34 selected cells can be used for PBPCT. The procedure is time consuming and expensive; it requires complex organization at laboratory level, and the benefit of CD34 selection with regard to T-cell depletion and tumor purging still needs to be proven. However, CD34+ selection is likely to open new perspectives in transplantation medicine.

Adolescent↗
PubMed1996

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia.

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient's immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51+/-6% for group A and 61+/-7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.

Adolescent↗
PubMed1995

[Flow cytometry identification of CD34-positive cells].

In the present study three clinical applications of flow-cytometric quantification of CD34-positive cells in the field of blood and marrow transplantation are evaluated. By daily determination of CD34-positive cells in the peripheral blood after mobilization of stem cells with chemotherapy or growth-factors it is possible to set the optimal time for collection of the transplant material. Thereafter the yield of CD34-positive cells within the harvested material is determined. Finally, the efficacy of positive CD34 selection using a biotin-avidin column is evaluated. Initial experience is presented here.

Antigens, CD↗
PubMed1995

Immature B cells from human and mouse bone marrow can change their surface light chain expression.

The capacity of bone marrow-derived surface immunoglobulin-positive (sIg+) human and mouse immature B cells, generated either in vitro or in vivo, to change their light (L) chain expression, has been assayed by the number of cells which change in vitro from one type of L chain to the other type, or to no sIg at all. Immature sIg+ B cells were generated in vitro from sIg- precursor cells from human or mouse bone marrow. The immature sIg+ cells expressed RAG-1. Human sIg+ cells expressed kappa and lambda L chains in ratios between 1:1 and 3:1, whereas in mouse cells, this ratio ranged from 10:1 to 20:1. Upon reculture of the human and mouse kappa+ sIg+ cells, about half of them remained kappa+, a quarter became lambda+, and another quarter became sIg-. Between 1 and 3% expressed both kappa and lambda chains. Of the human lambda+ cells, about two-thirds remained lambda+, only 1 to 2% became kappa+, while the other third became sIg-. Again, between 1 and 3% expressed both kappa and lambda L chains. These results indicate that expression of sIgM in the B cell membrane does not terminate L chain gene rearrangement, and that some order exists in kappa versus lambda gene rearrangements. Hence, human and mouse kappa+ immature B cells can become lambda+, but very few of the lambda+ cells can become kappa+, and both can become sIg-. Further, human CD10+/sIg+ kappa+ and lambda+ cells and mouse B220low/sIglow kappa+ cells enriched from bone marrow, i.e. immature B cells differentiated in vivo, changed their Ig phenotype upon in vitro culture, but in lower frequencies. By contrast, human and mouse mature B cells did not change their L chain or Ig phenotype. Hence, at least a part of the sIg+ immature B cells in bone marrow retain the capacity to change their L chain and Ig phenotype, and this capacity is lost when they become mature, peripheral B cells.

Adolescent↗
PubMed1995

Childhood NHL in Switzerland: incidence and survival of 120 study and 42 non-study patients.

Based on the Swiss Pediatric Oncology Group (SPOG) cancer registry data during 1981-1991, a high average incidence of 8 new NHL per million children younger than 15 years per year was found. Of 162 children with NHL registered in 1976-1991, 120 were study patients, i.e., officially registered and treated according to SPOG or Pediatric Oncology Group (POG) protocols, while 42 were non-study patients, i.e., patients not officially enrolled on protocols. Overall, 91 of 120 (76%) study patients remained alive. Seventy-nine study patients were treated according to older SPOG protocols, and 53 (67%) of these survived, while 38 of 41 (93%) study patients treated according to newer POG protocols remained alive (P = 0.0068). Only 22 (52%) of the 42 non-study patients survived (P = 0.0001). There was no improvement if the survival of non-study patients before and since 1986 was compared. Population-based treatment results in Switzerland were similar to those in the United Kingdom. They provided an important base for the development of future treatment strategies.

Adolescent↗
PubMed1995

Does monozygotic twinning occur in mice?

Published reports suggest that the incidence of monozygotic twinning in women is increased after hormonally induced ovulation. Since some statistical evidence exists to indicate that monozygotic twinning may also occur in mice, we attempted to devise a mouse system in which the incidence of such twinning could be compared after spontaneous versus hormonally induced ovulation, in order to analyse the developmental basis of such an effect. We used phenotypic identity in litters segregating for ten genetic loci (not all independent) to indicate possible twin pairs. DNA finger-printing using three human minisatellite probes was then performed blind on these pairs and on sibling controls. From a total of over 2000 mice born, 40 apparently identical pairs were identified, on which DNA finger-printing was successfully carried out on 35 pairs. All proved to be derived from different zygotes. We conclude that monozygotic twin pairs are either extremely rare in the stock of mice that we studied, or have such reduced viability that their chance of surviving to weaning is low.

Animals↗
PubMed1995

Boys but not girls with T-lineage acute lymphocytic leukemia (ALL) are different from children with B-progenitor ALL. Population-based data results of initial prognostic factors and long-term event-free survival. Swiss Pediatric Oncology Group.

PURPOSE: In a population-based data registry of children with ALL, initial prognostic factors were analyzed with regard to long-term event-free survival. PATIENTS AND METHODS: From 1976-1991 the Swiss Pediatric Oncology Group (SPOG) observed 610 children and adolescents who were diagnosed with ALL before the age of 15 years, and who were prospectively treated according to different study protocols. Immunophenotyping of B-progenitor- or T-lineage ALL was possible in 573 children. Leucocyte count, age, and sex were compared with regard to immunophenotype of lymphoid cells and to event-free survival on Kaplan Meier curves by statistical analyses including multivariate analysis and the Cox regression backward elimination test. RESULTS: Of the 573 patients who were immunophenotyped 86.4% had B-progenitor ALL and 13.6% T-lineage ALL. The differences between B-progenitor ALL and T-lineage ALL with respect to initial white blood cell count, age and gender were significant. A comparison of event-free survival in children with B-progenitor ALL versus T-lineage ALL revealed significant differences in boys (p < 0.001) but not in girls (p = 0.183). Statistical tests showed gender to be an independent risk factor. CONCLUSION: The long-term outcome following identical treatment of both genders was significantly better in girls with T-lineage ALL than in boys. Girls with T-lineage ALL, but not boys with T-lineage ALL, had a prognostic outcome similar to children with B-progenitor ALL.

B-Lymphocytes↗
PubMed1994

[How long should cyclosporin be administered following bone marrow transplantation?].

After organ transplantation, life-long immunosuppression is mandatory to prevent rejection. This is not the case after allogeneic bone marrow transplantation (BMT). The mechanisms of tolerance are little understood and there is little data about the required duration of immunosuppression. In a retrospective study we analyzed the use of cyclosporine A (CyA) treatment in all BMT patients who where transplanted in Basel from 1979 to 1991. 243 patients with a median age of 26 (2-49) years received CyA to prevent graft-versus-host-disease (GvHD) and rejection. 206 patients had leukemia, 26 severe aplastic anemia and 10 a lymphoproliferative disorder. All were treated according to a common CyA regimen with initial parenteral administration followed by oral treatment for a year; after 1988 treatment duration was reduced to 6 months. Drug dosage was adjusted according to clinical symptoms, plasma levels and toxicity. At relapse of the original disease CyA was always withdrawn. Three months after BMT 96% were still on CyA. After 6 months 79%, after 1 year 61%, after 2 years 29%, after 3 years 18%, after 4 years 15%, after 5 years 8% and after 8 years 2% of patients were still taking CyA. All 20 patients who are still alive 10 years after BMT are off CyA. CyA was administered parenterally for a median of 31 (5-147) days. Oral treatment started at day 25 (4-28). The oral dose was reduced 5 (1-20) times, increased once (1-75) and finally discontinued after a median time lapse of 1 year (14d-8y).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Gender and response to antilymphocyte globulin (ALG) for severe aplastic anaemia.

We have evaluated the speed of haematological recovery in 103 severe aplastic anaemia (SAA) patients treated with antilymphocyte globulin (ALG) and followed at our institution for 3-15 years. We found that haemopoietic recovery was significantly delayed in six girls under the age of 10 years. This slow recovery in girls might be explained by their relative inability to release haemopoietic growth factors, granulocyte colony stimulating activity and burst promoting activity, compared to all other sex and age groups. This defect is not explained by disease severity at presentation and thus indicates a functional abnormality of monocytes/macrophages and T-lymphocytes in addition to the deficiency of haemopoietic stem cells. In a multivariate analysis, low factor production and low pretreatment reticulocyte counts turned out to be strong predictors of slow haemopoietic recovery. We conclude that young girls have a particular form of SAA characterized by low haemopoietic factor production and delayed recovery after ALG. They are preferential candidates for early bone marrow transplantation or, if they are not eligible, for treatment with recombinant human haemopoietic growth factors.

Adolescent↗
PubMed1992

[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Adolescent↗
PubMed1992

Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin.

One hundred and seventeen patients with severe aplastic anemia (SAA) were treated at our institution between 1976 and 1990 with antilymphocyte globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%. Twenty-six patients developed a late clonal complication: 11 had a myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal hemoglobinuria (PNH); two patients had both. The cumulative risk at 10 years is 42%. The development of MDS/PNH after SAA directly affects survival. The probability of being alive at 14 years is 81% +/- 10% for patients with stable disease and 36% +/- 13% for those with clonal evolution (P = .001). To look for predictive signs, we reevaluated peripheral blood and bone marrow cytomorphology at presentation, during regeneration, and in remission. We examined the peripheral blood values for hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity, erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces slow and incomplete recovery. Although in "remission," ALG patients have lower hemoglobin values, higher reticulocyte counts, lower granulocyte and platelet values, and a higher MCV and fetal hemoglobin than normal controls. They retain a reduced number of megakaryocytes and a persistence of atypical monocytes in bone marrow morphology as stigmata of their disease. Patients with late clonal complications show distinct morphologic abnormalities: patients with PNH have higher MCVs, higher granulocyte and reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower hemoglobin with an increased proportion of erythroblasts in the bone marrow in "remission." Patients who later developed MDS are not different from the total patient population at diagnosis. After therapy, these patients are characterized by the presence of ring sideroblasts and atypical monocytes during regeneration and by a persistent increase in MCV, a higher fetal hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during "remission." Thus, routine morphologic follow-up examination of blood and bone marrow can discover patients at risk for late hematologic complications after ALG therapy.

Adult↗