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Detection of two different cell populations in a child is a rare event. The following case of a dispermic chimera was diagnosed before surgery due to problems in blood group determination. A 2-year-old phenotypically male child was admitted for correction of a penoscrotal hypospadia and unilateral cryptorchism. During presurgical laboratory investigation, difficulties in blood group determination occurred. Blood group typing was performed by the DiaMed-ID Micro Typing System and by FACS. Additionally, cytogenetic analysis of lymphocytes and analysis of DNA polymorphisms in different tissues were performed. Two populations of red blood cells were detected, O cells accounting for 75% and B cells for 25%. Analysis of DNA-PCR polymorphisms in lymphocytes, nails, and in cells of the oral mucous membrane demonstrated a chimerism, with two alleles inherited from the father and one from the mother. A cytogenetic analysis of cultured lymphocytes showed a mosaic 46, XY/46,XX. Surgery revealed a prostatic utricle grade III, also called pseudovagina; genitography confirmed a vagina. Bilateral gonad biopsy showed a testis on one side and an ovary on the other. This case of chimerism represents a true hermaphroditism that most probably developed by double fertilization of one or more egg nuclei by two sperms.

In order to estimate the residual risk of transfusion-transmitted HCV infection, we have analyzed data from transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1990 to 1995. In Vienna, the seroprevalence (RIBA-confirmed third-generation anti-HCV tests) was 0.28% in first-time donors (FTD) and the incidence of seroconversion in repeat donors (RD) was 0.049 (per 100 person years) from 1994 to 1995. In Göttingen, the prevalence of a PCR-confirmed positive third-generation anti-HCV test was 0.22% in FTDs and the incidence was 0.093 (per 100 persons years). A continuous decline of the rate of anti-HCV-positive donations and donors was observed with first- and second-generation anti-HCV tests in the years 1990-1994. The introduction of the third-generation anti-HCV test resulted in increased numbers of anti-HCV positive repeat donors, mainly due to false-positive results. Only 9% of anti-HCV-positive repeat donors were either PCR positive or RIBA positive or or indeterminate. Based on a mathematical model which takes (a) the window period, (b) the false-negative rate of anti-HCV tests, and (c) human and operational errors into consideration, we have calculated the residual risk of HCV infection. We used a window period of 74 days, a sensitivity of 98%, and an error rate of .1%. The residual risk (for third-generation anti-HCV test-negative blood components) was calculated to be 1:9000 (95% confidence interval 1:16390-1:6210) and 1:4800 (95% confidence interval 1:40000-1:1320) for Vienna and Göttingen, respectively, in 1994 and 1995. Since this conservative approach does not take the impact of ALAT screening into account, the actual risk is probably lower.

In order to estimate the residual risk of transfusion-transmitted HIV infection we have analyzed the data from two transfusion centers in Austria (Vienna) and Germany (Göttingen) from 1985 to 1994. In Vienna, an incidence of 1:42,000 positive anti-HIV tests in repeat donors and a prevalence of 1:7000 in first-time donors were found in 1993. In Göttingen, the indicence was 1:67,000 and the prevalence 1:7900 from 1985 to 1993. Based on a mathematical model which takes (a) the window period and (b) the false-negative rate of anti-HIV tests, as well as (c) human and operational errors into consideration, we have calculated the residual risk of HIV infection. The residual risk (third generation anti-HIV test) was found to be 1:520,000 (95% confidence interval 1:1340,000-1:210,000), and 1:900,000 (95% confidence interval 1:2340,000-1:380,000) for Vienna and Göttingen, respectively, in 1993. Look-back studies from 1985 till 1994 revealed transfusion-transmitted HIV infections in three recipients (for 1.9 million donations in Vienna) and one recipient (for 160,000 donations in Göttingen) of blood components. Based on our model, as well as on prevalence and incidence rates of HIV infection, it is also possible to predict the efficacy of additional measures introduced to further decrease the risk of transfusion-transmitted HIV infection through blood components.

The HLA system encompasses approximately one thousandth of the human genome and contains a series of closely linked loci coding for molecules which provide the context for the recognition of antigens by T lymphocytes. Within the HLA system, several phenotypically expressed and genomic polymorphisms can be distinguished. These polymorphisms are described and the main objectives for the future research are discussed.

A method for the calculation of the probability of paternity for the HLA system using only the typing results from the child and the putative father, without taking into account the data of the mother, is presented. Furthermore, the usability of the formulas by Mayr and Pausch (Z. Immun.-Forsch. 150, 447 (1975)) for the computation of the chance of paternity exclusion in such cases is demonstrated.

In 19 patients with idiopathic adrenal insufficiency and in 19 controls, cellular (as measured by the migration inhibition test) and humoral (by means of immunoflourescence) immune reaction to adrenal antigens were investigated. Significant inhibition of migration was observed in 12 patients with adrenal microsomes; migration of mononuclear cells was however within normal range in 18 out of 19 controls. Adrenal antibodies could be detected in 11 (53%) of the patients. In a further series of investigations adrenal microsomes have been preincubated with specific antibody and used in migration inhibition tests. The migration indices observed with microsomes were compared to those obtained with microsomes preincubated with adrenal antibody. Migration inhibition with microsomes could be blocked by antibody in almost all antibody-positive patients. No uniform trend on the migration of mononuclear cells was found in the antibody-negative patients. A blocking of the cellular immune reaction by specific antibody seems likely. Possible mechanisms which could lead to such phenomena as well as the biologic significance of adrenal antibodies are discussed.

The HLA-A, B, C haplotype frequencies determined through family investigations in 500 unrelated individuals of the Viennese population were calculated, as well as the gene frequencies of 37 HLA determinants and the linkage disequilibria between the three HLA SD loci (HLA-A, HLA-B, and HLA-C). The existence of HLA-A, B, C superhaplotypes could be confirmed.

A 5-year-old male with multiple malformations (dwarfism, microcephalia with brachycephalic shape of skull, mongoloid lid axis, epicanthus, convergent strabismus, flat root of the nose, micrognathia, missing uvula, deformed low-set ears, hypoplastic genitals, and general hypotonia), severe mental retardation, and cerebral paroxysms caused by a partial monosomy (1)(q42 leads to qter) is described. This case is compared with other cases with a partial monosomy or ring-1 chromosomes.

In a series of 42 families with 101 children the linkage between HL-A and PGM3 could be confirmed (most likely recombination fraction for male equals 0.15).

The genetics of the serological defined SD antigens of the HLA system, which are governed by three closely linked loci (HLA-A, HLA-B and HLA-C) situated on the chromosome C6, are described. Regarding patermity testing, only the antigens coded by the loci HLA-A and HLA-B are used routinely up to now. Because of the strong linkage disequilibrium between these two loci, they cannot be considered as independent. The influence of the linkage disequilibrium on the calculation of the chance of paternity exclusion and of the plausibility of paternity is discussed and demonstrated in several examples.

After a survey of the genetics of the HLA system, the possibility to type bloodstains for HLA gene products is discussed.

Within a sample of 6107 non related subjects no dependency of the Gm-types from the Rh-phenotypes could be observed. These data as well as the results of linkage studies do not suggest the localisation of the Gm-loci on chromosome 1.

Humoral immunity to bacterial antigens was tested in 49 tissue typed patients with juvenile onset diabetes mellitus (JOD) and in 50 healthy controls. The number of patients with agglutinins to E. coli and staphylococci was significantly lower compared to controls (p less than 0.001, p less than 0.01 respectively). Missing antibody formation to pertussis and diphtheria toxoid could also be detected in a higher percentage of JOD patients than of controls (p less than 0.05; p congruent to 0.05, respectively). By contrast heteroagglutinins to sheep and rabbit erythrocytes were found in similar proportion in both groups and the values of immunoglobulin serum concentrations showed no difference between patients and controls. In addition no correlation between antibody formation and genes of the HLA complex was found. It is suggested that the severely reduced agglutinin formation to bacteria antigens might be partly responsible for susceptibility to bacterial infections in juvenile diabetics.

Classification of the hereditary motor and sensory neuropathies is discussed and findings reported in the recent literature are compared to our own findings in a kinship with autosomal dominant CMT. Previous studies in CMT-families with comparable slow nerve conduction velocities had shown positive linkage of this hereditary neuropathy to the Duffy blood group locus; however, blood group typing in the recently studied kinship excluded close linkage, which may indicate the existence of another sub-group in this entity. Testing of visually evoked potentials in this kindred demonstrated significant differences in P 100 latencies of the families of twin brothers. This intrafamilial difference may also be an expression of heterogeneity.

2 patients with 13- and C9-rings are reported. On reviewing the phenotypical features of the published ring carriers and comparing them with our results we do not find any characteristic similarities. This can be explained by cytogenetical and biological findings. We are therefore inclined to reject the existence of clear-cut ring chromosome syndromes.

In 21 informative families with 60 children, a possible linkage between HL-A and GLO was found (recombination fraction approximatively 0.15). The sequence of the loci on chromosome 6 might be GLO, HL-A, PGM3, MNSs.