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Biomedical subjects

H Grosse-Wilde

Publications and source records attributed to H Grosse-Wilde.

At least 145 records · Page 8Linked to original sources
PubMed1988

Significant association of acute lymphoblastic leukemia with HLA-Cw7.

Frequencies of all defined HLA-A, -B, -C (-DR) antigens were determined in 142 (59) Germans suffering from acute lymphoblastic leukemia (ALL) with differentiation of immunologically defined or age-related subgroups of the disease. A highly significant rise of the HLA-C locus antigen Cw7 was found in ALL patients, particularly those over the age of 11 in comparison with local German and Caucasian controls of the Ninth Int. Histocompatibility Workshop (WS). Only slight differences of HLA-Cw7 frequencies were observed within the four immunologically defined ALL subtypes of all or age-related patient groups. HLA-A, -B, or -DR antigens, as well as HLA-ABC three-locus haplotypes were similarly distributed in patients and their local or Caucasian controls. The results indicate HLA-linked genetic factors conferring susceptibility to ALL in adults, particularly those presenting with B-, T-, and Null-ALL.

Adolescent↗
PubMed1988

HLA-A,B,C,DR typing and 17-OHP determination for second trimester prenatal diagnosis of 21-hydroxylase deficient CAH.

In 18 families at risk for the HLA-linked, 21-hydroxylase deficient form of autosomal recessive congenital adrenal hyperplasia (CAH), prenatal diagnosis (PD) was performed using two methods: (1) HLA-A,B,C typing and in the latter 11 cases also DR typing of cultured amniotic fluid cells (AFC) using the standard microcytotoxicity assay, and (2) measurement of second trimester amniotic fluid 17-hydroxyprogesterone (17-OHP) concentration using gel chromatography and radioimmunoassay. The accuracy of the prenatal predictions was confirmed by postnatal HLA typing of umbilical cord blood lymphocytes and by clinical evaluation. In 16/18 families, both HLA typing of AFC and 17-OHP measurements proved informative for PD. The predictions of both methods were concordant in 14/16 families (88 per cent). In ten of these families, a normal fetus was predicted, and in four, an affected fetus; all pregnancies were carried to term and all predictions were confirmed postnatally. In 2/16 cases (12 per cent), however, the predictions were discordant: the prenatal HLA typing indicated an affected fetus, whereas the 17-OHP values predicted a normal fetus. Both pregnancies were continued and two healthy boys were delivered. The discordance proved to be due to a 'missed' HLA antigen in one case and to serologically cross-reactive HLA antigens in the second. Finally, in 2/18 cases, prenatal assessment of fetal genotype had to rely on HLA typing alone as 17-OHP measurement was not performed in one family and in the second family the 17-OHP values obtained were not informative due to inadvertent continuation of hormone therapy to the date of amniocentesis. In both cases, the HLA typing data accurately predicted a normal fetus. In conclusion, a combination of HLA typing of cultured AFC and 17-OHP measurements of amniotic fluid permits accurate prenatal diagnosis of CAH in most cases (88 per cent). In addition, the supplementary use of HLA-DR typing of AFC as presented here for the first time proved helpful in families with HLA-A,B homozygosity due to parental sharing of antigens and can be informative for identifying HLA-B/21-OH recombinant haplotypes.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Familial multiple sclerosis.

Siblings of patients with multiple sclerosis have an increased risk of developing the disease. In this report we describe 3 families with multiple affected members, representing the largest published aggregation of cases in first degree relatives. In the 2 families in which HLA tissue-typing was performed the affected individuals shared part of the haplotype HLA-DR2 (+ HLA-DQW1), BfS (+ C2C), C4A3, C4B1. The implications of these findings for the aetiology of multiple sclerosis are discussed.

Adolescent↗
PubMed1988

Recombination within the class III region by a double cross over event.

Analysis of class I, class II, and class III gene products of the human MHC in a Caucasoid family with four children gave evidence for a double crossing over event in monozygotic twins between the C2, Bf/C4A, C4B gene loci. In view of the small genetic distance between C2 and C4, a point mutation within the Bf locus must be considered alternatively.

Crossing Over, Genetic↗
PubMed1988

Treatment of acute graft-versus-host disease after HLA-partially matched marrow transplantation with a monoclonal antibody (BMA031) against the T cell receptor. First results of a phase-I/II trial.

As part of an ongoing phase-I/II trial, 2 patients received a 5-day treatment course with a murine monoclonal antibody (MAB) directed against the human T cell receptor (BMA031) as primary therapy of acute grade III skin and gastro-intestinal graft-versus-host disease (GvHD) occurring after allogeneic bone marrow transplantation (BMT). All MAB infusions were tolerated without side effects. A complete response of all symptoms of acute GvHD could be attained by MAB therapy under a continued baseline immunosuppression with cyclosporin (CSP), and both patients remain alive and disease-free at 7 and 8 months after therapy without evidence of chronic GvHD. Although the exact treatment scheme has still to be defined, we conclude that this MAB may be useful as primary therapy of acute GvHD. However, the potential hazards of 'in vivo' therapy with MABs directed against T lymphocytes call for a critical evaluation of this treatment modality.

Adult↗
PubMed1988

Heterogeneity in protein patterns of cells from terminal blast crisis in chronic granulocytic leukemia: discrimination between lymphatic and myeloid lineages.

Terminal blast crisis cells of chronic granulocytic leukemia are biochemically distinct. Triton-X-114 detergent phase lysates revealed that myeloid types express predominantly proteins of a 24 kd apparent molecular weight range, whereas lymphatic types do not express these molecules but a 55 kd protein band. These biochemical differences, observed in the poorly differentiated blast crisis cells, are also found in well differentiated hemopoietic malignancies such as chronic lymphatic leukemia, or in mature granulocytes isolated from healthy individuals. The results support the concept of the different lineages of blast crisis cells in chronic granulocytic leukemia but question the role of these proteins in cell differentiation. In addition, the presence or absence of these proteins provide a helpful tool for classifying blast crises of chronic granulocytic leukemia.

Antibodies, Monoclonal↗
PubMed1987

Acute myelofibrosis in megakaryoblastic leukemia with translocation between chromosomes 8 and 14.

In a 45-year-old woman with severe normochromic anemia (Hb 2.8 g%) an extensive myelofibrosis and infiltration of the bone marrow with small blasts was observed histologically. Cytochemical examination of the blasts showed a negative peroxidase and a strongly positive alpha-NE reaction. PAS reaction was slightly granular positive in the cytoplasmic protuberances of the blasts and in the platelets. Marker analysis yielded no evidence of lymphatic origin of the blasts. In flow-cytometric studies of 230,000 cells a homogeneous 2c blast population could be identified. Cytogenetic analysis revealed an abnormal pseudo-diploid karyotype characterized by 2 acrocentric marker chromosomes caused by a translocation of chromosomes 8 and 14, as usually seen in Burkitt type lymphoma. Finally the reaction product of platelet-specific peroxidase could be demonstrated in the perinuclear cisternae of the endoplasmic reticulum by electron microscopy. Highly elevated beta-thromboglobulin and platelet factor 4 plasma levels were also measured. Following an ineffective treatment with daunoblastine and ARA-C, the patient died of pseudomonas aeruginosa septicemia after having received high-dose ARA-C treatment.

Biopsy, Needle↗
PubMed1987

HLA-DR4 and Gm 1;21 haplotypes are associated with pseudolupus induced by venopyronum dragées.

The phenotypic frequencies of human major histocompatibility complex class I, II, and III antigens and immunoglobulin allotypes (Gm factors) were determined in 56 patients (55 women, 1 man) who had lupus-like disease induced by venopyronum dragées. The findings in these patients were compared with those of a control group. We found a significant increase of HLA-DR4 (57.1% versus 26.5%, relative risk [RR] 3.7) and a decrease of HLA-DR3 (3.6% versus 19.1%, RR 0.16) in the patient group. In addition, the haplotype Gm 1;21 (60.7% versus 32.9%, RR 3.2), and the phenotype Gm 1,3;5,21 (46.4% versus 25.8%, RR 2.5) were significantly increased. Both the haplotype Gm 1;21 and the phenotype Gm 1,3;5,21 are associated with HLA-DR4 in pseudolupus patients but not in controls. The coincidence of HLA-DR4 and Gm 1;21 markedly increases the risk of acquiring pseudolupus (RR 6.9). We conclude that the pathogenesis of pseudolupus is influenced by at least 2 independent genetic factors. A similar HLA association has been described in hydralazine-induced lupus, and this suggests a common pathogenic mechanism.

Adult↗
PubMed1987

Statement on the nomenclature of dog C4 allotypes.

As a collaborative work of three laboratories the polymorphism of the canine fourth complement component (C4) was studied in a total of 131 unrelated dogs from different breeds and mongrels. Using high voltage electrophoresis followed by an immunoblotting technique, we detected eight distinct variants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of canine C4 showed an additional heterogeneity of the alpha and gamma chains which resulted in a total of 11 variants in the population studied. So that more precise information concerning the respective C4 allotypes will be available, a nomenclature is proposed designating not only the migration pattern of the C4 variants in agarose gels but also the heterogeneity of the C4 chains observed in SDS-PAGE.

Alleles↗
PubMed1987

Allogeneic bone marrow transplantation for acute leukaemia or chronic myeloid leukaemia in the fifth decade of life.

To determine the influence of advanced age on long-term survival after allogeneic bone marrow transplantation (BMT), the probability of survival and the frequency of transplantation-associated complications were analysed retrospectively in 20 patients with acute leukaemia (AL) or chronic myeloid leukaemia (CML), who were 40-49 years of age (median 44.5 years) at the time of transplant. The results of this patient group were compared to those of 32 patients aged 30-39 years (median 33.5 years) with AL or CML, who also underwent BMT during the same period of time. The overall actuarial survival of the two age groups was comparable with 44% and 41% at 5.9 and 5.6 years, respectively. Patients with standard risk criteria (i.e. HLA-genotypically identical sibling donor, 1st chronic phase of CML or 1st remission of AL) showed a higher probability of survival in both groups (62% at 5.9 years in older patients and 59% at 5.5 years in younger patients, respectively). In contrast, actuarial survival in patients who underwent BMT at an advanced stage of their disease or with marrow from a partially HLA-compatible donor was significantly inferior (P = 0.04). The cumulative incidence of acute and chronic graft-versus-host disease was low in older patients (27%), who received marrow from an HLA-identical sibling donor. The most frequent cause of death was interstitial pneumonia, occurring in seven of the older patients (35%) and in seven of the younger patients (22%). This difference, however, was not statistically significant. Our results indicate that allogenic marrow transplantation in the fifth decade of life might be associated with a tolerable risk of transplantation-related complications. This treatment modality may therefore be regarded as first-line therapy for patients in 1st remission of AL or first chronic phase of CML, who show a normal performance status. The same applies to older patients in advanced stages of disease, since the results are comparable to those achieved in the younger patient group.

Acute Disease↗
PubMed1987

Joint report of the Third International Workshop of Canine Immunogenetics. II. Analysis of the serological typing of cells.

Using a standardized microlymphocytotoxicity assay, seven international laboratories evaluated 144 anti-dog lymphocyte antigen (DLA) sera in 319 mixed breed and 152 Beagle dogs. The workshop confirmed the serological definitions for DLA-A2, A3, A9; DLA-B4, B5, B6, B13; DLA-C11(Cwl); and C12(Cw2). Two new specificities were assigned to the DLA-A locus (Aw14 and Aw15) in only the mixed breed dogs. A third specificity (Cw3), was assigned to the DLA-C locus. The antigen and gene frequencies of these alleles differed between the two groups of dogs, but the frequencies of the "blank" were similar in both groups. Future international collaborations will be necessary to definite more completely the polymorphisms of the major histocompatibility complex (MHC) of the dog. Those efforts will benefit from the standard serological test established in this workshop.

Alleles↗
PubMed1986

Joint report of the Third International Workshop on Canine Immunogenetics. I. Analysis of homozygous typing cells.

The Third International Workshop on Canine Immunogenetics involved 80 potentially DLA-D homozygous typing cells obtained from dogs of various breeds and submitted from five laboratories in Europe and the United States. Mutual reactivity of all cells was studied in mixed leukocyte cultures, and stabilized relative responses were used for analysis. Intralaboratory and interlaboratory comparisons of results suggest that a stabilized relative response of 30% represents an acceptable parameter for "typing responses" indicating phenotypic DLA-D identity of stimulator and responder cells. Using this criterion, 10 clusters of homozygous typing cells were defined and accepted on an international level, and they were assigned the specificities Dw1 to Dw10. At least six additional (provisional) specificities were recognized that were well characterized within individual laboratories but require additional testing before workshop specificities can be assigned. These data show that DLA-D typing is feasible and represents a useful tool in the genetic analysis of the canine major histocompatibility complex. Much work is needed to confirm the present results in family studies, to determine gene frequencies, and to analyze at a molecular level the antigens responsible for mixed leukocyte culture reactivity.

Animals↗
PubMed1986

Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs.

Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. In addition, it could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data presented may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells from histocompatible immunized donors.

Animals↗