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Biomedical subjects

H Grosse-Wilde

Publications and source records attributed to H Grosse-Wilde.

At least 19 recordsLinked to original sources
PubMed1992

Molecular detection of genetic defects in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a study of 27 families.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21-OHase) deficiency is inherited as an autosomal recessive trait. Patients can present with the salt wasting, simple virilizing or a non-classical form of the disease. The gene for P450C21, the enzyme carrying 21-OHase activity, has been mapped to the major histocompatibility complex on chromosome 6p. Using molecular hybridisation techniques we have studied the genetic defect in 27 families with one or more affected offspring diagnosed and treated at the University Hospital of Essen. DNA samples were digested with restriction endonuclease TaqI, PvuII, BglII, and EcoRI and analysed by Southern blot hybridisation with the cDNA probe pC21/3c. Eleven of 40 haplotypes associated with the salt wasting form were found to have a large deletion of 30 kb affecting the 5' end of the active 21-OHase gene and the 3' end of the closely linked pseudogene. Results in another 11 cases are compatible with gene conversion; 18 cases were not informative. The 30 kb deletion was associated with a combination of the HLA antigens Bw47 and DR7 in 7 of 11 cases. In the haplotypes with gene conversion, no linkage disequilibrium to HLA antigens was found. No apparent gene alterations were detected in simple virilizing and non-classical haplotypes. The direct detection of the genetic defect in 55% of the salt wasting haplotypes may help to improve predictive testing in families with CAH.

Adrenal Hyperplasia, Congenital↗
PubMed1992

Soluble HLA class I and class II concentrations in commercial immunoglobulin preparations.

Soluble HLA class I (sHLA-ABC) and class II (sHLA-RQP) molecules were quantitated in 16 commercially available immunoglobulin (Ig) preparations by enzyme-linked immunosorbent assays. Whereas three Ig preparations contained no detectable sHLA-ABC, all preparations showed concomitant sHLA-RQP molecules. There was a considerable variability with regard to the individual sHLA concentrations. For sHLA-RQP the values exceeded that found in human plasma of healthy individuals, suggesting that the extraction procedure may concentrate not only Ig, but also HLA class II molecules. Based on the total dosage of intravenously administered immunoglobulins (i.v.Ig), contaminating sHLA molecules may become immunogenic. Furthermore, sHLA molecules are discussed in terms of participation in the well-known immunomodulating effects of i.v.Ig therapy.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Quantitation of the human component C4: definition of C4 Q0 alleles and C4A duplications.

We determined the C4 plasma concentrations of 48 genotypically CA4- and C4B-defined unrelated individuals from 34 families with a total of 196 members by an enzyme-linked immunosorbent assay using Rg:1,2 (C4A) and Ch:1 (C4B) specific monoclonal antibodies. The results obtained allowed the establishment of rules for the detection of C4 Q0 alleles in the heterozygous form and of C4A gene duplications. In the present study seven homoduplications of the C4A 3 allotype were defined which had not been detected by allotyping. This procedure allows the simple, reliable, and quick determination of Rg:1,2 and Ch:1 plasma levels which are not influenced by daily rhythms of C4 production.

Alleles↗
PubMed1992

Enumeration of T, B and natural killer peripheral blood cells of patients with multiple sclerosis and controls.

The median percentages of peripheral blood immunoglobulin-positive (Ig+) lymphocytes (8%, n = 46), CD8+ (12%, n = 49) and CD57+ cell numbers (5%, n = 37) of patients suffering from multiple sclerosis (MS) were significantly (p less than 0.05) lower than the values of age- and sex-matched healthy individuals (Ig+ cells: 13%, n = 46; CD8+ cells: 17%, n = 49; CD57+ cells: 9%, n = 37). Comparison of calculations on decreased peripheral blood cell counts and increased brain cell counts in MS patients revealed that sequestration of blood cells into the MS brain is a possible explanation of these findings.

Adult↗
PubMed1991

[Maintenance of remission in acute myeloid leukemia by allogeneic or autologous bone marrow transplantation].

Over a 10-year period 120 patients (58 women, 62 men; median age 33 [14-53] years) with acute myeloid leukaemia were treated by allogenic (n = 90) or autologous bone marrow transplantation to maintain remission. After a median observation time of 41 (11-126) months 64 patients (53%) remain alive without recurrence of leukaemia. Ten years after allogenic transplantation performed during the first complete remission the probability of disease-free survival is 50 +/- 8%, as compared with 50 +/- 9% at 4.5 years after autologous transplantation. Significant factors influencing disease-free survival after allogenic transplantation during the first complete remission were the time interval up to the onset of remission and the length of the remission before transplantation. The chance of disease-free survival after allogenic transplantation in the second complete remission does not so far differ from the results achieved by transplantation in the first complete remission. The risk of recurrence after autologous transplantation in the first complete remission (47 +/- 10%) is significantly higher than that following allogenic transplantation (18 +/- 10%, P less than 0.0001). Acute graft versus host reactions occurred in 16% and chronic reactions in 36% of patients after allogenic transplantation. The mortality was 38% after allogenic transplantation and 7% after autologous transplantation.

Acute Disease↗
PubMed1991

High-dose 1,2,4-triglycidylurazol given in regimens preparatory to bone marrow transplantation. A preclinical pharmacology study.

To elucidate its potential role in the framework of bone marrow transplantation, we studied the toxicologic and pharmacologic properties of high doses of the triepoxide derivate 1,2,4-triglycidylurazol (TGU) in a preclinical dog model. Dose-dependent and dose-limiting gastrointestinal toxicity occurred in a dose range between 40 and 75 mg/kg, with the lethal dose for 50% of animals (LD50) being estimated at 60 mg/kg. Severe and life-threatening hematologic toxicity developed at all dose levels examined but was generally reversible. The combination of TGU and total-body irradiation produced synergistic gastrointestinal toxicity, necessitating reductions of the TGU dose by 50% as compared with the single-agent dose. In contrast, the combination of TGU and high-dose busulfan resulted in no apparent nonhematologic synergistic toxicities. The immunosuppressive properties of TGU given in this combination enabled sustained histocompatible allogeneic marrow engraftment in three of four animals. The pharmacokinetics of TGU were not influenced by prior total-body irradiation or high-dose busulfan. We conclude that the myelotoxic, pharmacologic and immunosuppressive properties of high-dose TGU observed in this preclinical model seem to render the drug particularly suitable for use in regimens preparatory to bone marrow transplantation.

Animals↗
PubMed1991

Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human alpha/beta T cell receptor.

A murine IgG2b monoclonal antibody directed to the constant part of the human alpha/beta T cell receptor (BMA031) was investigated in a pilot study as an initial treatment for acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation. The treatment protocol consisted of 5 mg BMA031 on 5 consecutive days with continuation of the prophylactic baseline immuno suppression using cyclosporin. Seven patients with grades II-III acute graft-versus-host disease were entered on the protocol and six patients completed the full treatment course. Mild to moderate acute adverse reactions to the first BMA031 infusion occurred in three patients. A nearly complete decline of circulating T lymphocytes was observed during BMA031 therapy, but the T cells returned to pretreatment values within 1 week after the last infusion. Serum pharmacokinetics of free antibody best fitted to a two-compartment open model with a mean initial half-life of 6 h and an estimated mean terminal half-life of 40 h. One patient developed antimurine antibodies of the IgM subclass. In five patients a complete and sustained resolution of all disease manifestations was attained, while in one patient a temporary response of skin involvement with aGvHD was noted. These results indicate that BMA031 can be safely administered as initial treatment of aGvHD. The therapeutic responses observed warrant its further clinical evaluation in this setting.

Acute Disease↗
PubMed1991

Fc receptor blocking antibodies after active immunization for the treatment of recurrent spontaneous abortion.

In a prospective study 140 couples who had at least three spontaneous abortions (RSA) were studied for the presence of Fc receptor blocking antibodies detected by the erythrocyte antibody rosette inhibition (EAI) assay, for anti-paternal cytotoxic antibodies (APCA), and for mixed lymphocyte culture inhibiting (MLCI) antibodies before and after active immunization with paternal lymphocytes. The comparative analysis revealed the EAI assay to possess a higher sensitivity than the APCA and/or MLCI tests in monitoring the specific immune response after active immunization. The success of pregnancy in EAI positive post-immunization patients was not influenced by the presence or absence of APCA or MLCI. In the light of a successful pregnancy outcome of 85.7% (n = 37) in this study we conclude that the monitoring of Fc receptor blocking antibodies is useful in active immunization protocols for RSA patients.

Abortion, Habitual↗
PubMed1991

Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-gamma).

In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-gamma (rIFN-gamma) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 micrograms rIFN-gamma three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN-gamma. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 micrograms rIFN-gamma. The increments peaked after 2-4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rIFN-gamma. The correlation observed between induction of beta-2-microglobulin and soluble HLA class I proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies.

Carcinoma, Renal Cell↗
PubMed1991

Recognition of monocyte-associated antigens in the dog.

Canine pregnant sera were investigated for monocyte-specific cytotoxic antibodies against a cell panel from 50 unrelated dogs. Contaminating DLA and DLB reactivity was removed by absorption on a random pool of purified lymphocytes. Two monocyte-associated antigens were recognized by two independent clusters of antisera; the existence of further antigens is suggested. In preliminary segregation studies, the inheritance of these determinants in linkage with DLA could not be observed.

Animals↗
PubMed1991

Quantitation of soluble HLA class II molecules by an enzyme-linked immunosorbent assay.

In order to quantify soluble HLA-DR,DQ,DP molecules (sHLA-RQP) an enzyme-linked immunosorbent assay was developed utilizing two monoclonal antibodies specific for HLA-DR,DP (Tü35) and HLA-DQ (Tü22) gene products, respectively. Highly purified HLA class II molecules isolated from a lymphoblastoid cell line were used for calculation of exact sHLA-RQP protein values. Circadian variations of sHLA-RQP plasma levels were studied in 7 healthy probands showing no significant deviations; measurements in 4 probands at intervals between 4 and 6 weeks revealed that sHLA-RQP levels remain relatively stable. The population analysis of 209 unrelated, HLA-typed healthy donors resulted in an average protein concentration of 1.53 +/- 2.44 micrograms/ml plasma for sHLA-RQP. Four out of 209 probands (= 1.9%) had no detectable sHLA-RQP. Significant associations of high or low sHLA-RQP levels to particular HLA-DR or -DQ specificities were not observed. However, plasma derived from HLA-DR9 positive had the highest and from HLA-DR8 positive donors the lowest mean sHLA-RQP values. By comparing HLA identical with two-haplotype-different siblings we found no evidence that sHLA-RQP plasma levels are under genetic control of the HLA complex or closely linked genes. Furthermore, soluble HLA class I plasma concentrations in 100 probands analyzed showed no correlation to those of sHLA-RQP.

Antibodies, Monoclonal↗
PubMed1990

Improved test to identify heterozygotes for congenital adrenal hyperplasia without index case examination.

In an attempt to improve detection of heterozygote carriers of the gene for congenital adrenal hyperplasia (21-hydroxylase deficiency; CAH) 64 families with at least 1 affected member (72 homozygotes and 191 clinically healthy subjects) were studied by HLA genotyping and by the single-dose corticotropin stimulation test. Plasma samples were drawn immediately before corticotropin and 60 min after its injection, and they were analysed simultaneously for eight adrenal steroids by radioimmunoassay after extraction and automated gel chromatography. Heterozygosity was defined as the presence of one HLA haplotype in common with the affected relative. Of the various basal and corticotropin-stimulated steroid levels and their ratios, the ratio of 17-hydroxyprogesterone to 11-deoxycorticosterone after corticotropin had the greatest power to discriminate between heterozygotes and normal relatives; that ratio was significantly higher in the heterozygotes (n = 116) than in the normal relatives (n = 75) and there was no overlap between the groups (range 12.2-214 vs 1.2-11.9). Thus, it is possible to detect all CAH heterozygotes without examining the index case by means of specific steroid analysis.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Heterogeneity in protein patterns of CGL blast crisis cells: discrimination between lymphatic and myeloic lineages.

Studies on cell-membrane-bound proteins in the human hematopoetic system revealed that the expression of certain peptides is restricted to the differentiation lineage. We applied discontinuous polyacrylamide gel electrophoresis of triton X-114 lysates to identify such proteins for a new diagnostic approach in human leukemia. A polypeptide with an apparent molecular mass range of 24 kd (p24) was found predominantly in cells of chronic granulocytic leukemia (CGL), myeloic type of blast crisis, and normal granulocytes. The data presented here suggest a role of this protein in the biology of malignant cells in chronic granulocytic leukemia throughout the course of the disease.

Biomarkers, Tumor↗