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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 253 records · Page 14Linked to original sources
PubMed1987

Genetic heterogeneity in X-linked agammaglobulinemia complicates carrier detection and prenatal diagnosis.

X-linked agammaglobulinemia (XLA) is a severe antibody deficiency disease reflecting an arrest of B lymphocyte differentiation at the level of precursor B cells. The disease is inherited in an X-linked recessive mode. In a single eight-generation pedigree the XLA gene was mapped to the Xq21.3-Xq22 area of the X chromosome. The data establish close linkage of the XLA locus to the DXS17 restriction fragment length polymorphic (RFLP) marker locus (the lod score exceeding 6 at phi = 0). A series of RFLP markers around the DXS17 locus provided an RFLP haplotype of use in genetic counselling within this pedigree. In one other pedigree a phenotypically identical disease was inherited but was accompanied by a high frequency of recombination with the DXS17 locus, which made localisation of the gene at the DXS17 locus highly unlikely (lod score less than -3). This genetic heterogeneity complicates genetic counselling within particular pedigrees, especially when the localization of the XLA gene involved in those pedigrees has not been established.

Agammaglobulinemia↗
PubMed1987

Desaturation-producing factor present in the tissue, blood, and urine of cancer patients.

Patients with liver neoplasms have a significantly lower stearic to oleic ratio (SI) in tumour (x = 0.36) vs non-tumour liver tissues (x = 0.75; P less than 0.001). The SI of circulating erythrocytes is lower in cancer patients (n = 100; X = 0.69) than noncancer patients (n = 50; x = 1.45) and normal subjects (n = 50; x = 1.5) (p less than 0.001). It was also found that urine protein extracts from cancer patients reduce the SI of cultured cell membrane (n = 10; x = 0.74) as compared to urine from noncancer patients (n = 10; x = 1.02; p less than 0.001). This study suggests that patients with cancer release a desaturation-producing factor from the malignant cells into the systemic circulation and subsequently into the urine. The observed increased unsaturation (oleic acid) in the circulating erythrocytes can be useful in the diagnosis and postoperative monitoring of cancer patients.

Adult↗
PubMed1986

Efficient singlet oxygen inactivation of firefly luciferase.

Firefly luciferase is inactivated by singlet oxygen at near diffusion controlled rates, 1.9 X 10(9) M-1 s-1, based on direct comparison with the oxidation of L-histidine. The inactivation kinetics are multiphasic. Inactivation is inhibitable by NaN3. Surface-separated-sensitizer (SSS) system in which singlet oxygen is produced above an air gap separating the reaction solution from the Rose Bengal sensitizer, ensuring only Type II reactions, was compared with a Sensitox II system in which the polymer bound Rose Bengal is contained in the reaction solution and both Type I and Type II reactions can occur. A slight stabilization is afforded by MgSO4.

Histidine↗
PubMed1986

Microsomal chemiluminescence of benzo[a]pyrene-7,8-dihydrodiol and its synthetic analogues trans- and cis-1-methoxyvinylpyrene.

The cis- and trans-methoxyvinylpyrene (MVP) analogues of benzo[a]pyrene-7,8-dihydrodiol (7,8-diol) produce specific microsomal chemiluminescence comparable to that produced from 7,8-diol in Aroclor-induced rat liver microsome preparations. The chemiluminescence quantum yields, emission spectra, and the concentration and the temporal kinetics of these three substrates have been examined. Radiolabelled 7,8-diol and t-MVP exhibit significant covalent binding (more than 14%) to microsomal protein when metabolized enzymatically. The extreme quenching of the dioxetane chemiluminescence by both microsomes and phosphatidylcholine, as a model phospholipid, implies that despite the low quantum yield (approx. 10(-8) photons per substrate molecule) for microsomal chemiluminescence of these substrates, a significant fraction of their microsomal oxygenations may proceed via a dioxetane pathway.

Animals↗
PubMed1986

Immunoglobulin heavy chain gene rearrangements in X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) appears to involve a defect in human B lymphocyte differentiation which is manifested at the pre-B cell stage. The defect segregates as an X-linked recessive trait but is not a single genetic entity. IgM-producing B cell clones were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells of patients with the XLA defect linked to the DXS3 and DXS17 chromosomal loci. Individual XLA B cell clones were demonstrated to have rearrangements of the JH regions of both immunoglobulin VH region loci. The rearranged JH regions of the B cell clone ALA 19 were molecularly cloned and their nucleotide sequence was determined. Both JH-associated rearrangements (designated 191 and 192) resulted from the juxtaposition of variable (VH), diversity (D) and joining (JH) segments (VHDJH rearrangements). The 191 rearrangement employed a VH segment belonging to VH subgroup III and a JH4 segment. The 192 rearrangement employed a VHII and a JH6 segment. The D191 and D192 segments encompassed 21 and 28 nucleotides, respectively, and showed little homology to each other or to previously reported human D sequences. Surprisingly, both VHDJH complexes had open reading frames. However, in accord with principles of allelic exclusion, only the 191 allele was detectably expressed in the total RNA of the cell. A possible mechanism for the lack of expression of the 192 allele is discussed. We conclude that the DXS3-DXS17-linked XLA defect does not preclude VH to DJH rearrangements or the expression of VH containing heavy chain molecules.

Agammaglobulinemia↗
PubMed1986

Physical separation and functional interaction of Kluyveromyces lactis and Saccharomyces cerevisiae ARS elements derived from killer plasmid DNA.

Two DNA fragments which have autonomously replicating sequence (ARS) activity in both Saccharomyces cerevisiae and Kluyveromyces lactis have been isolated from the K. lactis kl killer plasmid. One fragment (Kla1) is 700 base pairs (bp) in length and plasmids carrying it are mitotically unstable in both hosts. In K. lactis, this instability leads to colonies having a 'nibbled' phenotype when grown on selective media and appears to be the result of inefficient plasmid segregation. The other fragment (Kla2) is an artificial junction fragment of 1100 bp which was produced during the cloning procedure. Kla2 has been divided into two sub-fragments Kla2A and Kla2B which have, respectively, ARS activity in K. lactis and S. cerevisiae but not the other species. This indicates that these two closely related yeasts have different sequence requirements for ARS activity. Kla2B contains a perfect match to the S. cerevisiae ARS consensus but Kla2A does not. Both Kla2A and Kla1 share a 10 bp sequence as the sole region of homology between them. This sequence, 5'TCATAATATA3', is tentatively offered as defining the ARS consensus sequence for K. lactis.

Base Sequence↗
PubMed1986

Mapping of a gene for X-linked agammaglobulinemia and evidence for genetic heterogeneity.

X-linked agammaglobulinemia (XLA) is a severe humoral immunodeficiency disease of man. The inheritance of the disease is X-linked recessive. Female carriers can not be distinguished by immunologic assays. We investigated the localization of the disease gene on the X chromosome, utilizing nine polymorphic X chromosomal markers. In a single eight generation pedigree we found close linkage of the disease gene to the restriction fragment length polymorphism (RFLP) recognized by the DNA probe p19-2; the maximum lod score was 3.30 at a recombination fraction of 0.06. Addition of the lod scores for p19-2 obtained from seven other XLA pedigrees did not show the expected increase of the total score. This suggested genetic heterogeneity. We used the p19-2 marker as a reference point to search for pedigrees which had the disease gene at a different location. One pedigree provided a lod score of -3.14 at a recombination fraction of 0.06 with the p19-2 marker. We postulate that XLA is not a single genetic entity.

Agammaglobulinemia↗
PubMed1986

Heterogeneity in the map distance between X-linked agammaglobulinemia and a map of nine RFLP loci.

In nine family pedigrees in which X-linked agammaglobulinemia (XLA) is segregating, a multi-point linkage analysis has been carried out. In each family, the map distance, d, between XLA and a fixed point in a known map of nine RFLP loci on the X chromosome was estimated by calculating the log likelihoods, L(d). Using a new method, the 10-point likelihood was approximated by appropriately combining three 4-point likelihoods. Homogeneity tests (admixture tests) were performed showing clear evidence for heterogeneity of XLA.

Agammaglobulinemia↗
PubMed1986

Molecular characterization of three HLA class II molecules on DR4 and DRw9 haplotypes: serologic and structural relationships at the polypeptides level.

By using alloantisera, three distinct HLA-D/DR region-encoded class II molecules were identified from cells carrying the HLA-DR4 and DRw9 haplotypes. Both DRw-53 and DQw3 molecules that bear the "supertypic" specificity were isolated independently from the DR antigen. The light chains of the DR4 antigens from different HLA-D types were distinct from one another, whereas the DRw53 molecules had identical charge and molecular weight in both heavy and light chains. On the other hand, the DQw3 molecules from the DR4 cell lines (Dw4 and Dw 10) were apparently identical but were polymorphic at least in the light chains among the DR4, DR5, and DRw9 haplotypes. In addition, monoclonal antibodies which specifically precipitate DR4 and DQw3 molecules have been isolated. The variable extent of homogeneity and diversity of three class II molecules may aid in our understanding of the role of class II antigens in the human immune regulation.

Antibodies, Monoclonal↗
PubMed1985

A pulse radiolysis investigation of the oxidation of the melanin precursors 3,4-dihydroxyphenylalanine (dopa) and the cysteinyldopas.

The unstable quinones of 3,4-dihydroxyphenylalanine (dopa) and the most abundant cysteinyldopa isomers (2S-, 5S- and 2,5S,S'-) have been generated rapidly via disproportionation of their respective semiquinones prepared pulse radiolytically by one-electron oxidation of the corresponding dopas with azide radicals. Dopaquinone decays via a base-catalysed unimolecular cyclisation yielding leucodopachrome which, under the present conditions, is immediately oxidised by remaining dopaquinone to form dopachrome and dopa back again. Addition of cysteine increased the rate of dopaquinone decay and precluded dopachrome formation. By contrast, the cysteinyldopa quinones decayed via an acid-catalysed unimolecular cyclisation involving the cysteine side chain to form a cyclic quinone-imine observed directly for the first time. These quinone-imine intermediates subsequently rearranged to more stable phenolic benzothiazine isomers. The addition of cysteine had little effect on cysteinyldopa quinone decay and did not prevent quinone-imine formation. The absorption spectra, extinction coefficients and rate constants for formation and decay of these various transient species involved in melanisation are reported.

Cyclization↗