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Biomedical subjects

T Kristensen

Publications and source records attributed to T Kristensen.

At least 145 records · Page 8Linked to original sources
PubMed1982

The inhibitory effect of Zn2+ on poly(ADP-ribose) polymerase activity and its reversal.

Zn2+ inhibits purified poly(ADP-ribose) polymerase (50% inhibition at 10 microM). Furthermore poly (ADP-ribose) polymerase present in nuclei and metaphase chromosome clusters is also inhibited by Zn2+. The inactivated enzyme could be re-activated by dithiothreitol. The concentration of Zn2+ needed to affect the enzyme activity in the organelles is sufficiently low for it to have a possible role in controlling the activity of this chromatin-bound enzyme.

Animals↗
PubMed1982

Genetics of complement C4. Two homoduplication haplotypes C4S C4S and C4F C4F in a family.

A family in which two homoduplicated C4 haplotypes (or supergenes) segregate is described. One haplotype C4F*3 C4F*2.2 is composed of two C4F alleles and the other C4S*5.1 C4S*1 of two C4S alleles. The C4F duplication haplotype is a partial inhibitor of the Rodgers antigen, and judged from our family and population material, it seems to be rather frequent and associated with HLAB*35, Bf*F, and HLAD/DR*1. The C4S duplication haplotype is Rg(a-) and is not identified in individuals without another S, Ch(A+) variant.

Adult↗
PubMed1982

Planned immunization of human volunteers with HLA-DR incompatible lymphocytes I. Serological aspects.

Aiming at the production of anti HLA--DR test sera, eight healthy human volunteers were immunized by repeated intradermal injections of lymphocytes which were selected to be incompatible for one HLA--DR antigen, and matched as well as possible for HLA--A,--B,--C antigens. One out of 3 recipients immunized exclusively against HLA--DR produced lymphocytotoxic HLA-DR antibodies. The remaining 5 recipients were immunized against 1 or more HLA--A,--B,--C antigens in addition to one HLA--DR antigen. After 3 immunizations, 3 of these reacted with strong HLA--A or --B antibody production; however, only one showed a parallel anti HLA-DR antibody response detectable by complement dependent lymphocytotoxicity. Testing of the recipient sera in the antibody dependent cell-mediated cytotoxicity (ADCC) assay revealed that 6 of the 8 recipients did react early to the immunizations with HLA specific antibody production. However, in spite of repeated booster injections it was not possible to obtain more than the above-mentioned 2 sera with HLA--DR antibodies strong enough to react in the lymphocytotoxicity microtechnique.

Antibody Formation↗
PubMed1982

Human B-blast specific target determinants in CML: a family study.

Human B blast specific target determinants, selectively identified on PWM stimulated purified B lymphoblasts by in vitro generated CTLs, have previously been studied in the population and showed association to and inclusion of HLA-DR geneproducts. This report indicates that B blast target determinants are products of genes which in a codominant mendelain way segregate with the HLA haplotypes in 4 selected families. Furthermore tests of families with HLA-B/D, DR and HLA-D, DR/GLO recombinations show that human B blast specific target determinants are coded from loci (locus) in the HLA-D region, between HLA-B and GLO.

B-Lymphocytes↗
PubMed1982

Monoclonal mouse anti-I-Ak and anti-I-Ek antibodies cross-reacting with HLA-DR supertypic and subtypic determinants rather than classical DR allelic specificities.

Thirty monoclonal alloantibodies (mAB) against mouse Iak antigens have been derived by fusion of mouse myeloma and spleen cells from A.TH (Ks Is Dd) mice immune to A.TL (Ks Ik Dd) lymphoid cells. Analysis of: (i) their reactivity (using 125I labelled protein A cell binding or cytotoxicity assays) on lymphoid cells from selected mouse strains with recombinant H-2 haplotypes; and (ii) the spatial arrangement of the specificities detected on the Iak molecules (studied by means of competitive inhibition of binding of radio-labelled monoclonal antibodies), permitted the identification of various epitopes present either on the I-Ak molecules (some of which were apparently identical to the conventional Ia.2, Ia.1 and Ia.19 specificities), or the I-Ek molecule (some being apparently analogous to the Ia.7 specificity) or on both I-Ak and I-Ek products. These mAB were tested in two different panels of human T and B lymphocytes. Panel (a) consisted of 28 Caucasian unrelated individuals, highly selected with regard to HLA-DR specificities, while panel (b) concerned 53 random HLA-A, B, C, DR typed individuals. The standard complement dependent lymphocytotoxicity microtechnique of histocompatibility workshop VIII was used throughout. All mAB were negative on resting T cells. Testing on B cells produced three patterns: 1) ten mAB did not react with any B cell tested; 2) four mAb reacted with all the panel cells; 3) sixteen mAb reacted with different sets of the panel indicating identification of polymorphic determinants. However, the strength of positivity obtained with a majority of single mAb varied considerably in the panel, suggesting identification of cross-reactive determinants. This necessitated the use of individual assignment criteria for each mAb. Following this procedure, 8 mAb were ascertained as reacting with HLA-DR supertypic determinants, 6 with associations to MT1, MT2, or both. Eight mAb reacted with HLA-DR subtypic determinants (more restricted than a classical DR allele). No mAb were ascertained, reacting exquisitely with acknowledged HLA-DR allelic specificities.

Alleles↗
PubMed1982

Competitive inhibition of T-cell mediated lympholysis by platelets.

Platelets are known to possess serologically detectable HLA-A, B, C (class I) antigens, but not HLA-DR (class II) antigens. We have used platelets as non-labelled (cold) competitors for cell-mediated lympholysis directed against determinants on PHA (3 days) and PWM (7 days) 51Cr-labelled (hot) lymphoblasts, i.e. T and B lymphoblasts, respectively. It is found that platelets are able to incompletely inhibit cytolysis against T-lymphoblasts, but not B-lymphoblasts. The inhibition is immunologically specific in the sense that only platelets autologous to the original responder cell do not. The immunogenetic specificity of platelet blocking is unknown at present, since no allogeneic third party platelets have been investigated. It is further found that platelets do not inhibit cytolysis by cytotoxic lymphocytes previously qualified to identify HLA-non A, B, C, D/DR determinants on T-lymphoblasts. Like in serology, platelets have to mature (greater than or equal to 7 days) in order to obtain optimal results. Since platelets are easy to procure and maintain their reactivity for months by simple storage in saline at 4 degrees C, platelets may be used to screen for cell-mediated lympholysis against HLA-class I, II or "new" determinants.

Binding, Competitive↗
PubMed1981

The HLA-D system: at least two loci and four distinct phenotypic traits per haplotype. Introduction to component typing in families and population by primed lymphocyte typing.

Using a number of intrafamilial PLTs raised against identical HLA haplotypes it has been possible to construct a model in an informative family defining the HLA-D region as a genetic system. This system consists of at least two regions separated by a recombination between HLA-D and GLO. In relation to the site of recombination, a minimum of one centromeric and three telomeric components can be identified per haplotype. - Fourteen PLTs raised and defined within the family were subsequently tested in a Caucasian population (n = 84) and in 13 unrelated, complete families. - It is concluded that the hypothetical model proposed for the HLA-D regions as a genetic system of linked loci, coding at the cell surface for associated but distinct components (at least four per haplotype), allows for typing of the components of the HLA-D system of any given haplotype. Serological typing of HLA-D components should, in the near future, provide a more convenient way of establishing component phenotypes than the present use of primed lymphocyte typing reagents. Among the components isolated, some have a high association with the classic alleles defined either by homozygous typing cells or DR serology. Others form the basis of cross-reactivity but their presence does not interfere with standard typing. Others, however, seem by their mere presence to be responsible for false assignments. - The concept of HLA-D as a genetic system clarifies many of the inconsistencies observed with a one-locus system.

Chromosome Mapping↗
PubMed1981

Clones of human cytotoxic T lymphocytes derived from an allosensitized individual: HLA specificity and cell surface markers.

By planned immunization of a volunteer, two stable (greater than or equal to 6 months), specific, alloreactive cytolytic T-cell clones have been established from his peripheral blood lymphocytes. One clone reacts with all serologically defined HLA-Cw3 cells from our panel, whereas the other defines a split within the serological HLA-B40 specificity. The two cytotoxic clones are SmIg-negative, E-rosette positive, EA and EAC rosette-negative, HLA-A, -B and -C- positive, and also HLA-DR- or 'Ia like'-positive. In addition, they present very similar patterns of iodinated cell surface molecules as analysed by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), contrasting with that of an EBV cell line derived from the same donor.

Adult↗
PubMed1981

Typing by cytotoxic lymphocytes. Genetics of HLA-non-A, B, C determinants - family studies.

Some CTLs recognize HLA-structures in a different way than antibodies, i.e. they may identify other epitopes than antibodies or may define genetically distinct structures. From population studies, in vitro educated CTLs were selected giving rise to significant lysis on PHA-lymphoblasts in the absence of the sharing of HLA-A, B, (C) determinants between stimulator and target lymphocytes. Based on pair-wise correlations these CTLs form 3 clusters, identifying structures associated to HLA-markers. Subsequent testing in 14 complete families of greater than or equal to 4 children allowed the observations: (1) CML-traits assigned on the basis of single CTLs often segregated in a non-mendelian way or independent of HLA. (2) Assignment made on the basis of CTL-clusters segregated with HLA. (3) in 2 informative HLA-B/D, DR recombinant families, CML-traits segregated with HLA-B. (4) No haplotype could be assigned more than one CML-trait.

Cytotoxicity, Immunologic↗
PubMed1981

A comparison of purified poly(ADP-ribose) polymerases from Ehrlich ascites tumor cells, pig thymus, and HeLa S3 cells.

Poly(ADP-ribose) polymerases from Ehrlich ascites tumor cells, pig thymus, and HeLa S3 cells were purified by chromatography on DNA-agarose and Blue Sepharose. A molecular mass of 112000 Da was found for all three polymerases. Fragmentation of polyacrylamide-gel-embedded polymerases with cyanogen bromide, and subsequent analysis of the fragments by polyacrylamide gradient gel electrophoresis, showed great similarities with regard to fragment sizes. The amino acid composition of the pig thymus enzyme was very similar to that of the polymerase from Ehrlich ascites tumor cells, and the terminal amino group appeared to be blocked. The HeLa polymerase electrofocused in two peaks at pH 8.8 and 5.5, while the Ehrlich ascites tumor cells and the pig thymus enzyme focused in single peaks at pH 9.4 and 9.6 respectively. Removal of residual DNA by treatment with hydroxyapatite abolished these differences in apparent isoelectric points; all three polymerases focused at pH 9.8. No important differences were found with regard to the effect of a number of substances on the synthesis of poly(ADP-ribose). Apparent Michaelis constants for NAD of 41 microM, 48 microM, and 34 microM were found for polymerase from Ehrlich ascites tumor cells, pig thymus, and HeLa S3 cells, respectively. All these results indicate that the three polymerases, which represented the major poly(ADP-ribose) polymerase activity in the organisms investigated, are closely related proteins.

Animals↗
PubMed1980

Poly(ADP-ribose) polymerase from Ehrlich ascites-tumour cells. Amino acid composition, N-terminal analysis and chemical cleavage of the purified protein.

Poly(ADP-ribose) polymerase was purified from Ehrlich ascites-tumour cells by two novel methods. Analysis for amino acid composition revealed a high percentage of acidic amino acids or their amides, and of basic amino acids. N-Terminal analysis with dansyl chloride revealed no terminal amino acid, indicating a blocked N-terminal amino group. Analysis by gel electrophoresis of protein treated with 3-bromo-3-methyl-2-[(2-nitrophenylthio)-3H-indole, under conditions where selective cleavage of the polypeptide chain at tryptophan residues is obtained, showed six major peptide bands.

Amino Acids↗