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The complete DNA sequence of a DR beta chain cDNA encoding the DRw12 allele has been determined. The sequence of this DRB1 allele reveals a structural relationship to the group of other DRB1 genes found on DRw52 haplotypes, such as DR3, -w11, -w13, -w14, and -w8. The structural similarities among this group of alleles are particularly evident in the first hypervariable as well as in the 3' untranslated region. The second hypervariable region contains a unique sequence not identified in any other DRB1 allele. The third hypervariable region appears to have arisen by gene conversion events involving two DRB1 chain genes, DR7 and DR1 or DR2/Dw21.

Two consanguineous Caucasoid HTCs, DHI and FPA, were investigated, the latter having an unusual HLA-DR/DQ(DC) association. Both these HTCs typed clearly as HLA-DRw11. However, while DHI typed as DRw11/DQw3(DC4) as expected, FPA typed as DRw11/DQw1(DC1) instead. Although extremely rare in Caucasoids, DRw11/DQw1 is a common pattern of association in Nigerian Negroids. Southern blots of DNA extracted from EBV cell line derived from FPA, hybridized with HLA-DC alpha and HLA-DC beta probes, confirmed this unusual DRw11/DQw1(DC1) association. In addition the DC alpha probe showed a unique additional restriction fragment length polymorphism (8 kb) attributable to the DX gene in the FPA DNA. When DHI and FPA were used as stimulators in MLC, the patterns to typing responses obtained were not completely concordant although they overlap to some extent. For this reason FPA has been locally designated Dw'F5', distinct from Dw5. Furthermore, the HLA-DQ antigens of the responder cells were not necessarily the same as those of the HTCS to which they gave typing responses (FPA and DHI). Functional studies using these two HTCs showed that the DQ(DC) antigens probably have no direct lymphocyte activating properties but rather have a regulatory role in controlling responses to allodeterminants in MLC.

Leukemic and normal hemopoietic cells were examined with the monoclonal anti-bodies DA2 and Genox 353 for the presence of HLA-DR and DR-linked (DC/MB) determinants, respectively. Although most non-T acute leukemias and leukemic cell lines expressed the monomorphic DR determinant detected by DA2, fewer than expected expressed the DR-linked polymorphic specificity detected by Genox 353. TdT+ lymphoid precursors from normal bone marrow were also DA2+ but Genox 353-. T cells and thymocytes which were DA2-, Genox 353- became DA2+, Genox 353+ after activation in vitro. Immunoprecipitation using DA2 and Genox 353 gave bands on polyacrylamide gel-electrophoresis which were of different molecular weights. In addition, DA2 could absorb out Genox 353 determinants from a cell lysate whereas Genox 353 could not absorb out DA2 determinants. It is concluded that DA2 and Genox 353 detect HLA-DR and DR-linked (DC1/MB1) determinants, respectively, and that these are differentially expressed on hemopoietic cells during differentiation.

Deliberate inhalation of volatile substances is a common and harmful phenomenon among young persons around the world. Clinical and cytogenetic studies were performed in 35 children (33 boys and 2 girls) chronically habituated to inhalation of volatile agents, with the aim to define whether this practice is associated with chromosome abnormalities and if so to what extent. A significant increase in the rate of chromosome abnormalities and in the frequency of sister chromatid exchanges (SCE) was found in sniffers over the values in controls (p less than 0.001). Clinical, socioeconomic, and cytogenetic findings are discussed.

The frequencies of the HLA-DR and -DQ antigens, including those of the new specificities "DRBr" and TA10, were established in a random panel of 286 British Caucasoids. The most frequent DR antigens were DR2, DR4 and DR7. The DR-DQ antigen associations were examined and the only heterogeneity found was with DR7 which was found to be associated predominantly with DQw2 but also with DQw3. The DR4's were subdivided into those positive and those negative for TA10 and DR4-TA10 was found to be associated with HLA-B44.

Human macrophage-like accessory cells were analyzed as they emerge in the absence of extrinsic antigens during fetal development. Monoclonal antibodies to monocytes/macrophages were used in combination with antibodies to HLA class II molecules. In the yolk sac and mesenchyme sampled at wk 4 to 6 of fertilization age, cells with dendritic morphology formed two populations distinguishable by phenotypic criteria: type i (majority) carried both macrophage-associated (RFD7+) and monocyte-associated markers (UCHM1+) but no detectable HLA-DR antigen, and type ii (minority) constitutively expressed class II (HLA-DR and -DP) but no RFD7 and UCHM1. The emergence of this heterogeneity preceded the formation of both thymus and bone marrow. During additional development, type i and type ii cells seeded to different microenvironments and underwent some additional phenotypic changes. Cells of type i, the RFD7+ population with high lysosomal (acid phosphatase) activity, were seen in the thymic cortex, marginal zone of lymph nodes, splenic red pulp, and in the midst of erythropoietic activity within the bone marrow. These cells were UCHM1- and class II-. Cells of type ii formed the population of HLA-DR+, RFD7- interdigitating cells, early inhabitants of T cell areas in the developing thymic medulla, lymph nodes, spleen, and tonsil. The Type ii cells that had already settled in their nichès expressed not only HLA-DR and -DP but also HLA-DQ, and another class II antigen identified by the antibody RFD1, which shows the restricted tissue distribution of HLA-DQ, but is governed by genes that are outside of and telomeric to the HLA-DQ region (or HLA-DR). Finally, subpopulations of macrophages (RFD7+, acid phosphatase-positive) in the fetal gastrointestinal and hepatic systems were HLA-DR+; the latter appear to include precursors of Kupffer cells in the developing liver.

The present study was carried out in order to assess the genetic component in a group of sterile or infertile couples from a latin american population. During a six-year-period, 258 patients were investigated. Sixty two per cent of the cases were studied for sterility and 38% for infertility. It was found that 34% had genetic pathology. In infertile couples the frequency of chromosome abnormalities was 2.8%; when sterility was also considered this frequency was 11.6%. Chromosome variants were found in 11.4% of the sterile patients and in 8.8% of the infertile cases.

The present paper describes a family with daughter and son affected with clinical characteristics of Pierre Robin's anomaly. The pedigree suggests an autosomal recessive inheritance pattern. The authors mention that in order to have more genetic evidence on this trait, an extensive study of families, with at least one proband should be made for a correct genetic analysis.

HLA-A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n = 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The results obtained show a decreased frequency of HLA-Aw19 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA-B18 and DR5(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw19 may confer some degree of resistance to the development of ALL and that the HLA-B18 and/or DR5 antigens may be resistance factors for the development of AML.

We have previously shown that HLA-class II antigens have a differential expression on acute myeloblastic leukaemia (AML) blasts. These cells express HLA-DR molecules but the HLA-DQ antigens are undetectable. In this paper we study the expression of HLA-DR and HLA-DQ antigens, using monoclonal antibodies (MoAbs), on normal cells of the myelomonocytic lineage: the common myelomonocytic progenitor (CFU-GM) and the monocytes, by techniques of inhibition of CFU-GM growth and double immunofluoroscence, respectively. The results show that HLA-DR and HLA-DQ antigens are differentially expressed on normal myelomonocytic cells. While HLA-DR molecules are expressed on CFU-GM and on the majority of peripheral blood monocytes, HLA-DQ antigens are not expressed on CFU-GM and only present on a subpopulation of monocytes. This data further confirms that HLA-DR and HLA-DQ molecules are coded by different genes with independent regulation of the gene expression not only on myeloid leukaemias but also on normal cells of the myelomonocytic lineage.

Blood lead and erythrocyte zinc-protoporphyrin levels were studied in 45 male adults exposed to lead (traditional home-factory pottery) and compared with two control populations. These two variables are well correlated in all the studied populations. Delta-aminolevulinic acid levels in urine (ALA-U) were significantly higher in the exposed group. Hemoglobin concentration (Hb), hematocrit (Hc) values and clinical data were also considered. We conclude that the zinc-protoporphyrin method here used is a simple reliable field test of the selection of individuals who need more detailed clinical investigation.