p hakenberg - Academia.edu (original) (raw)

Papers by p hakenberg

22. Hämophilie-Symposion Hamburg 1991, 1992

Die Ubertragerdiagnostik bei der Hamophilie A wird in Familien mit isoliert auftretender Hamophil... more Die Ubertragerdiagnostik bei der Hamophilie A wird in Familien mit isoliert auftretender Hamophilie A ganz entscheidend vom Geschlechtsverhaltnis der Mutationsraten beeinflust. Wenn Mutationen uberwiegend in mannlichen Keimzellen auftreten, wird es wahrscheinlich, das in der Familie eines isolierten Hamophilie A-Falls die Mutter Ubertragerin ist, da die Neumutation bei einem ihrer mannlichen Vorfahren stattfand. Wenn aber Neumutationen uberwiegend in weiblichen Keimzellen auftreten, so kann diese sehr wohl bei der Mutter stattgefunden haben, welche dann keine Ubertragerin ware.

Summary Carrier detection tests were carried outin119families withhemophilia A byusing thedataobt... more Summary Carrier detection tests were carried outin119families withhemophilia A byusing thedataobtained with currentDNA techniques (e.g., RFLPanalysis anddirect identification ofmutations), conventional carrier detection tests(e.g., factor VIII:C andvon Willebrand factor antigen), andpedigree information. Onthebasis ofthis data, we estimated the sexratio ofmutation frequencies withthree completely different methods and compared theresults. Since theclassical indirect method derived fromHaldane issubstantially influenced by reproductive fitness (f), the sexratio ofmutation frequencies was estimated forbothf= .3andf= .5,resulting inamale:female mutation ratio of5.37(95%confidence interval 2.16-13.02) and3.26(95%confidence interval 0.97-8.73), respectively. According totheequilibrium-independent indirect method formulated byRosendaal etal., themale:female ratio was estimated tobe3.4(95%confidence interval 1.18-8.81). Since currentDNA techniques provide information on thegrandparental or...

Bone marrow transplantation, 1998

Several CB-specific prerequisites have to be taken into consideration to deal with the increasing... more Several CB-specific prerequisites have to be taken into consideration to deal with the increasing number of stem cell transplants using multiple HLA mismatched umbilical cord blood (CB) specimens. Since CB represents a limited and expensive resource it demands an optimal allocation. Optimal CB allocation can not be optimal based solely on 'first come - first serve' basis, since frequently several CB specimens are simultaneously suitable for more than one patient. Furthermore, the immediate availability of CB gives rise to an above average proportion of urgent search requests for patients who need a transplantation urgently. Thus continuing reservation and release of a CB specimen has considerable influence on the stem cell transplant prospects of other patients. To avoid and/or solve allocation conflicts present in a much higher incidence than in the bone marrow donor setting a global co-ordinated allocation of cord blood specimens is of major advantage for these patients. T...

American journal of human genetics, 1993

Carrier detection tests were carried out in 119 families with hemophilia A by using the data obta... more Carrier detection tests were carried out in 119 families with hemophilia A by using the data obtained with current DNA techniques (e.g., RFLP analysis and direct identification of mutations), conventional carrier detection tests (e.g., factor VIII:C and von Willebrand factor antigen), and pedigree information. On the basis of this data, we estimated the sex ratio of mutation frequencies with three completely different methods and compared the results. Since the classical indirect method derived from Haldane is substantially influenced by reproductive fitness (f), the sex ratio of mutation frequencies was estimated for both f = .3 and f = .5, resulting in a male:female mutation ratio of 5.37 (95% confidence interval 2.16-13.02) and 3.26 (95% confidence interval 0.97-8.73), respectively. According to the equilibrium-independent indirect method formulated by Rosendaal et al., the male:female ratio was estimated to be 3.4 (95% confidence interval 1.18-8.81). Since current DNA techniques...

Klinische Pädiatrie, 1999

To date, human umbilical cord blood (CB) has been employed successfully in well over 1000 allogen... more To date, human umbilical cord blood (CB) has been employed successfully in well over 1000 allogeneic (unrelated and sibling) stem cell transplantations. Because of primary limitations in volume and cell numbers, over 90% of these transplantations were performed in children. Therefore requests for well standardised cord blood units of high quality are now increasing constantly. Examination and standardisation of unrelated and related cord blood stem cell preparations and banking as well as their biological characterisation was already initiated in Düsseldorf in 1992. Hitherto a total of 3236 CB samples with a mean volume of 89 +/- 25 ml, a mean total number of nucleated cells (NC) of 10 +/- 5 x 10(8) and a mean number of CFU-GM of 6 +/- 5 x 10(5) have also been validated by haematological, immunological and microbiological criteria. In addition to that, 97 directed CB donations of siblings with a clinical indication have been characterised and banked along the same lines. All CB units were collected from the umbilical cord vein immediately after vaginal full term delivery or caesarean section, then frozen and stored in liquid nitrogen. 1940 CB units were stored unseparated, the other 1296 were volume reduced using Hetastarch (HES) with a mean recovery of 85 +/- 13% of the nucleated cells, 86 +/- 12% and 84 +/- 13% for CFC and CD34+ cells, respectively. Only 5.0 ml of a CB sample is required for routine laboratory testing as there are HLA-class I typing, HLA-class II typing by sequence specific oligonucleotide probes (PCR-SOP), ABO typing, sterility control, assessment of progenitor and stem cells by colony forming assays, and CD34+ status as well as certain viral infections such as CMV, Hepatitis B, C, HIV, Parvo B19 by PCR technology before releasing the CB unit for transplantation. For apparent viral infections, maternal sera obtained at birth were tested for HBsAg, anti-HBc, anti-HCV, -HAV-(IgG, IgM), -HIV-1-2, -EBV- (IgG, IgM), -HTLVI-II, -CMV (IgM, IgG), toxoplasmosis and syphilis. Within the last three years a total of 4860 preliminary searches and 680 extended unit reports were submitted to the CB bank Düsseldorf by fax or World Wide Web. So far 68 unrelated and 3 related CB units were delivered. From these 70 have been transplanted in 30 different transplant centres world-wide. Until now the evaluation of the first 53 unrelated CB-transplantations was performed together with the EUROCORD transplant registry. Three patients were excluded from the analysis, since they received an unrelated CB-transplant for non-engraftment after previous allotransplants. The median patient age of these 50 patients was 5.0 years (range 0.3-44), the median weight 18 kg (range 4-70 kg). The majority of the patients transplanted for malignancies (66%) suffered from ALL (n = 19), AML (n = 7), CML (n = 4) and lymphoma (n = 2) with two third (75%) in an intermediate (2nd CR) or advanced stage of disease (> 2nd CR); 13 patients had metabolic diseases and immunodeficiencies and three had aplastic anaemia. All CB samples as well as the patients' blood samples were typed in Düsseldorf for HLA-class I by serology confirmed by PCR-SSP and by high resolution DNA typing for HLA-DRB1 and HLA-DQB1 alleles. 96% of the 50 patients receiving unrelated CB were mismatched at one or more HLA-antigens. 41 of the 50 patients transplanted with unrelated CB from Düsseldorf were evaluable for engraftment with an overall engraftment rate of 83%. According to the defined criteria of EUROCORD, 9 of the 50 patients were not evaluable for engraftment, since they died before day 60. The present median follow-up time is 14 months (1.4-38). The Kaplan-Meier estimate of survival at one year is 42 percent. The three paediatric patients after sibling CB transplantations (ALL, amegakaryocytic thrombocytopenia and CML) are alive with a follow-up time of 350, 379 days and 531 days. (ABSTRACT TRUNCATED)

International Journal of Gynecology & Obstetrics, 2000

To date, hematopoietic stem and progenitor cells from human umbilical cord blood (CB) have been e... more To date, hematopoietic stem and progenitor cells from human umbilical cord blood (CB) have been employed in approximately 90 allogeneic (56 sibling and 34 unrelated) matched and mismatched transplantations worldwide with easy and successful restoration of hematopoiesis. Requests for stem cell preparations from CB will continue to increase. Thus, as a pilot study, the examination and standardization of unrelated cord blood-derived stem cell preparations and banking as well as their biologic characterization were initiated. Up to October 1995, a total of 574 samples [mean volume 'Bone Marrow Donor Center (with Cord Blood Bank and Transplantation Immunology,

Human Immunology, 2000

Allelic matching within the HLA-DRB1 and-DQB1 loci significantly improves the clinical outcome of... more Allelic matching within the HLA-DRB1 and-DQB1 loci significantly improves the clinical outcome of hematopoietic stem cell transplantation. Consequently, allelic typing of these loci is strongly recommended for the unrelated stem cell donor selection. In this study, the HLA-DRB1,3,4,5 and-DQB1 alleles of 231 patients and their corresponding 821 nonrandom potential stem cell donors were determined to define compatible donor/recipient pairs. Highly accurate HLA typing data were achieved by PCR-SSOP and a combination of group specific PCR-SSP and subsequent sequencingbased typing of nearly the whole second exon of each locus. The alleles DRB1*07, *09, and *10 were analyzed by PCR-reverse dot blot hybridization instead of sequencing. Additionally, DRB1 homozygosity was verified by temperature gradient gel electrophoresis. The identified 2104 HLA-DRB1 and HLA-DQB1 alleles as well as data on HLA-DRB3,-DRB4, and-DRB5 alleles were applied to a statistical program and absolute and relative delta values of DR/DQ linkages were calculated. The achieved data on the HLA-DRB1 allele distribution and on DR/DQ associations in terms of subtypes significantly ensure the typing reliability, since rare allele combinations will result in further investigations. Furthermore, detailed data on the DR/DQ allele associations allow estimations of the number of HLA-A,-B, and-DR matched unrelated stem cell donors necessary for the identification of DRB and DQB subtype identical donors.