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Biomedical subjects

M H Breuning

Publications and source records attributed to M H Breuning.

At least 145 records · Page 8Linked to original sources
PubMed1987

Improved early diagnosis of adult polycystic kidney disease with flanking DNA markers.

A new polymorphic DNA marker for the diagnosis of autosomal dominant adult polycystic kidney disease (APKD) has been identified. The new marker, 24-1, flanks the APKD gene on the side opposite to the alpha globin on the short arm of chromosome 16. When both DNA polymorphisms bracketing the gene are informative the reliability of prenatal and presymptom diagnosis of polycystic kidney disease in non-recombinants (92% of cases) is more than 99%.

Adult↗
PubMed1987

A study of genetic linkage heterogeneity in adult polycystic kidney disease.

The mutation for adult polycystic kidney disease (APKD) has previously been localised to chromosome 16 by the demonstration of genetic linkage with the loci for the alpha-chain of haemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on only nine families so that the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purposes of detection of the disease, and complicate the characterisation of APKD at the molecular level. Therefore further families were studied to address this question. A total of 28 northern European pedigrees were analysed, all apparently unrelated, and with origins in England, Scotland, Holland and eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the APKD locus in this population.

Adult↗
PubMed1987

Human alpha-globin maps to pter-p13.3 in chromosome 16 distal to PGP.

Fibroblasts from a fetus with an unbalanced karyotype 46(XY), -16,+(16qter-16p13.3::4q31.1-4qter) were found to possess only one allele at the 3' hypervariable region (3'HVR) close to the alpha-globin locus and two alleles at the PGP locus. This places the alpha-globin locus at the very tip of 16p, distal to PGP.

Chromosome Banding↗
PubMed1986

Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis.

Adolescent↗
PubMed1986

Acute nonlymphocytic leukemia 5 years after treatment with cisplatin, vinblastine, and bleomycin for disseminated testicular cancer.

The combination of cisplatin, vinblastine, and bleomycin (PVB) was used to treat a 25-year-old man for disseminated testicular germ cell cancer, leading to a complete remission. Acute nonlymphocytic leukemia (ANLL), resistant to chemotherapy, developed 5 years later. The secondary nature of this ANLL was corroborated by the detection of nonrandom chromosomal aberrations in bone marrow cells of chromosomes, 7, 5, and 3. This is one of the first reports of possible leukemogenic activity of PVB treatment when applied without additional irradiation or alkylating agents.

Acute Disease↗
PubMed1986

A study of genetic linkage heterogeneity in adult polycystic kidney disease.

The mutation for APKD has previously been localized to chromosome 16 by the demonstration of genetic linkage with both the alpha-chain of hemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on a limited number of families, and the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purpose of detection of the disease and complicate the characterization of the APKD mutation at the molecular level. Therefore, further families were studied to resolve this issue. A total of 27 Northern European pedigrees were analyzed, all apparently unrelated and with origins in England, Scotland, Holland, and Eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha-globin and the disease locus in this population.

Adult↗
PubMed1984

A cloned cytotoxic T-lymphocyte (CTL) line recognizing a subtype of HLA B27.

The lymphoblastoid cell-line JY (HLA-A2,2;B7,7;C-; DR4,w6) was used to stimulate T cells from donor HG (HLA-A2,w23; B40,w44; Cw4; DRw6,7). Cloned CTL line were obtained by limiting dilution after tertiary stimulation. Strong cytotoxic activity on stimulator cells was found with all CTL clones obtained. One of the clones (HG-31 recognized a subtype of the HLA-B7 antigen. In this paper, we describe another long-term cloned CTL line (HG-61). This line, when tested on a panel of 107 target cells from unrelated individuals, recognized a subtype of HLA-B27 (B27 "K"). There was no significant association with any other HLA antigen. The cloned CTLs were T8+ and their cytotoxic activity could be blocked by the monoclonal antibody W6/32 which recognizes a framework determinant on HLA-A, -B, and -C molecules. In families, reactivity with cells of the CTL line (HG-61) segregated with HLA. It is concluded that the CTL line interacts with an antigenic determinant shared between the HLA-B7 antigen and JY and the subtype of HLA-B27 (B27 "K"), or detects products of a gene closely linked to HLA-B, not revealed by present-day serology.

Antibodies, Monoclonal↗
PubMed1984

Activation of cytotoxic T lymphocytes in HLA-A, -B and -C-identical responder-stimulator pairs. I. Variations in generation of anti-class-II CTL in primary mixed lymphocyte cultures.

Cytotoxic T lymphocytes were activated in primary one-way mixed lymphocyte cultures of cells matched for serologically defined HLA-A, -B and -C antigens. In 16 out of the 29 combinations mismatched for the HLA-D/DR antigens, cell-mediated lympholysis of the stimulator cells occurred. The specificity of 5 selected cytotoxic T lymphocytes was studied in detail. Three of these cytotoxic T lymphocytes recognize antigenic determinants associated with HLA-Bw35 (Breuning et al. 1984, II). The 2 other cytotoxic T lymphocytes failed to lyse T-target cells enriched by rosetting with sheep red blood cells, whereas target cells from the 'non-T' fraction were strongly lysed, indicating that antigenic determinants associated with Class-II HLA molecules were the targets recognized by these cytotoxic T lymphocytes. This notion was supported by a study of a panel of HLA-typed third-party target cells. One cytotoxic T-lymphocyte population preferentially lysed HLA-DR2-positive target cells. Family studies, including a family with a recombination between HLA-B and -D, showed that the target antigen recognized by the latter cytotoxic T lymphocyte segregated with DR2. The second cytotoxic T-lymphocyte population recognized a determinant associated with DRw8. However, in 13 of the 29 HLA-A-, -B- and -C-identical, D/DR-different combinations, cell-mediated lympholysis of stimulator target cells could not be detected, not even on enriched 'non-T' target cells. Thus, after primary mixed lymphocyte culture of HLA-A-, -B- and C-identical, HLA-D/DR-non-identical cells, cytotoxic T lymphocytes directed against sensitizing Class-II molecules can be detected in some combinations, but not in others.

Cell Adhesion↗
PubMed1984

Activation of cytotoxic T lymphocytes in HLA-A, -B and -C-identical responder-stimulator pairs. II. New subtypes of HLA-Bw35.

We compared five cytotoxic T lymphocytes raised by primary mixed lymphocyte cultures of HLA-A, -B and -C serologically identical Bw35-positive responder-stimulator combinations. When tested on a panel of third-party target cells, the reactivity pattern of these cytotoxic T lymphocytes allowed the distinction of three subtypes of HLA-Bw35. Cold-target inhibition experiments and analysis of CTL activity at the clonal level showed the existence of subsets of CTLs directed against distinct antigenic determinants associated with HLA-Bw35.

Cells, Cultured↗
PubMed1983

Biochemical analysis of variant HLA-B27 antigens.

Biochemical analysis of HLA-B27 antigens from individuals that are HLA-ABC identical by serology but distinct in CML typing establishes that two types of HLA-B27 can be defined biochemically. The division of HLA-B27 into a W type and a K type by CML typing correlates perfectly with the biochemical data. HLA-B27 K type possesses a more basic isoelectric point than HLA-B27 W type. Neuraminidase digestions of immunoprecipitated HLA-A,B antigens establish that the difference in isoelectric point between HLA-B27 K and HLA-B27 W is not due to differences in sialic acid content.

Electrophoresis, Polyacrylamide Gel↗
PubMed1983

Specificity of anti-HLA-B27 cytotoxic T lymphocytes.

Sub-types of HLA-B27 were detected by cytotoxic T lymphocytes (CTL) generated between HLA-A, -B- and -C-identical B27-positive individuals. We now report the specificity of six independent CTL's generated by mixed lymphocyte culture (MLC) of HLA-A, -B and -C serologically identical B27-positive responder and stimulator cells. Three CTL's recognize one sub-type, and three the other. The combined reactivity of all CTL's allows unequivocal "typing" of B27-positive cells for the two different sub-types B27K and B27W. The specificity of two CTL's was analysed by cold-target inhibition. The results indicate that (1) no further sub-types of HLA-B27 can be detected by the CTL's raised in these combinations; (2) the majority of the CTL's is directed against the B27 antigens; and (3) "extra reactions" on B27-negative cells are caused by a subset(s) of CTL's recognizing unknown antigens shared between stimulator and target cells. CTL's raised by stimulation of HLA-B27-negative responder cells with B27-positive cells of either sub-type lysed all B27-positive target cells indiscriminately. In cold-target inhibition, however, B27-positive cells, carrying the sub-type of B27 different from that of the stimulator, could not inhibit the lysis of cells bearing the stimulator sub-type of B27. This indicates the activation, in B27-negative responders, of at least two different groups of CTL clones, one directed against shared determinants of HLA-B27, and one against the HLA-B27 sub-type. Heterogeneity of the HLA-B27 antigen may have implications for studies on the well-known association between this antigen and various diseases.

Child↗
PubMed1982

Subtypes of HLA-B27 detected by cytotoxic T lymphocytes and their role in self-recognition.

In the present study cytotoxic T lymphocytes were generated in MLC of lymphocytes from two unrelated HLA-A, B, C-identical, B27-positive, but D/DR-different, individuals. These CTL were shown to detect subtypes of HLA-B27. CTL specific for influenza virus lysed infected target cells matched for HLA-B27 only when they shared the same subtype. This indicates that the two subtypes of HLA-B27 detected by CTL function also as distinct elements in a self-restricted CTL response. Both subtypes were found among patients with ankylosing spondylitis.

Cytotoxicity, Immunologic↗
PubMed1980

Constancy of cross-reactivity patterns in sera of individual mice during the anti-H-2 response.

H-2 alloimmunization evokes antibodies of differing cross-reactivity patterns among individual mice of one inbred strain. We investigated whether this is due to unknown variations at the time of bleeding or whether it remains constant for an individual mouse during long-term immunization. At various times during immunization, serum was collected from individual mice and it was tested on a panel of mouse and human lymphocytes. Sera from three donor-recipient combinations were examined. In some sera, a broadening of the cross-reactivity pattern occurred after prolonged immunization, but no major change in specificity was observed. We conclude that the differences in cross-reactivity pattern among sera from individual mice remain constant during the immunization period and do not reflect variations in the condition of the animals at the time of bleeding.

Animals↗