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Biomedical subjects

D M Gibson

Publications and source records attributed to D M Gibson.

At least 91 records · Page 5Linked to original sources

Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences.

The kappa light chain genes from two mutant hybridoma cell lines defective in kappa light chain synthesis were isolated and compared to the wild-type kappa light chain gene. In each case, the mutant kappa light chain genes were found to contain repetitive DNA elements in their intervening sequences that were not present in the intervening sequences of the wild-type kappa light chain gene. These elements were found to be related to the genes of intracisternal A particles. These results suggest that the decreased production of kappa light chain in the mutant cell lines is due to the presence of the intracisternal A particle-related genes.

Animals↗

A Comparison of Soybean Agglutinin in Cultivars Resistant and Susceptible to Phytophthora megasperma var. sojae (Race 1).

The amount of soybean agglutinin (SBA) detectable by radioimmunoassay in seeds of resistant cultivars to Phytophthora megasperma var. sojae was approximately twice that of susceptible cultivars. SBA was preferentially released at earlier times (6-9 hours) and in higher amounts in the imbibate from resistant cultivars as compared to susceptible cultivars. The lectin in the imbibate was immunologically identical to the seed lectin, indicating little or no proteolysis had occurred, and was active in hemagglutination. Binding of fluorescein isothiocyanate-labeled SBA to mycelial cell walls could be abolished by adding N-acetyl galactosamine or galactose. Purified SBA at concentrations of 150 to 300 micrograms inhibited mycelial growth by 50%, and the imbibate from Govan (resistant) cultivar was more inhibitory than the imbibate from Shore (susceptible) cultivar. Removal of SBA from the imbibate by affinity chromatography abolished the inhibition of mycelial growth, but the inhibition could be recovered from the eluant containing lectin.

Journal Article↗

Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus.

We previously showed that a chromosome 6 locus, IgK-Ef2, controls a pair of prominent bands in normal mouse light-chain isoelectric focusing profiles. Screening of myeloma light chains derived from BALB/c mice (an IgK-EF2 alpha strain) led to the identification of seven light chains cofocusing with the polymorphic bands controlled by IgK-Ef2. Complete sequencing of the variable (V) regions of four of the light chains indicates that they are all members of the same subgroup (Vk-1A) and they differ from one another by 1--3 substitutions. One of the protein differs from the prototype V-region sequence only in the deletion of a single residue at position 95 immediately preceding of J region. The other two differ from the protype V region by 3 (two framework [fr], one complementarity-determined [cdr]) and one (fr) residues, respectively. Complete V-region sequences of two closely related light chains derived from NZB mice (an IgK-Ef2b strain) indicate the NZB proteins are derived from a distinct Vk gene (Vk-1B), differing by four substitutions from the Vk-1A sequence. The results suggest that the IgK-Ef2 polymorphism may be a result of, at least in part, the loss of the gene(s) coding for the Vk-1A subgroups in IgK-Ef2b strains of mice. The nature of the sequence diversity found in the Vk-1A subgroup indicates that either it is coded by a repeated series of virtually identical genes or that somatic mutation of a single Vk-1A gene may give rise to substitutions in framework as well as cdr regions.

Amino Acid Sequence↗

Intraabdominal abscess after penetrating abdominal trauma.

In 57 (2.4 percent) of 2,416 patients undergoing laparotomy for penetrating abdominal trauma from 1977 to 1980, an intraabdominal abscess developed in the postoperative period. Preoperative antibiotic administration, careful closure of gastrointestinal tract perforation with diversion as necessary, and copious irrigation of the peritoneal cavity at the completion of surgery were common factors in all operations. Over 80 percent of penetrating wounds leading to abscesses occurred in the upper quadrants, and common risk factors included multiple intraabdominal solid organ injuries requiring open drainage, coupled with gastrointestinal tract perforation. Physician delay in the recognition of patients with intraabdominal abscess and in reoperation was a common problem.

Abdominal Injuries↗

Unique V kappa group associated with two mouse L chain genetic markers.

The C.C58 and C.AKR congeneic strains of mice differ from BALB/c at loci on chromosome 6 which govern kappa light chain variable region (V kappa) polymorphisms and the Lyt-2 and Lyt-3 alloantigens. Amino acid sequence analysis of light chains of myelomas induced in these strains revealed one light chain, C.C58 M75, that had an NH2-terminal serine and differed sufficiently from published V kappa sequences to define a new V kappa group, V kappa (Ser), apparently not expressed by BALB/c mice. Peptide map analysis indicated that the M75 light chain contained the IB-peptide marker, a V kappa polymorphism expressed by C.C58 but not BALB/c mice, which is determined by the IgK-Trpa allele present on chromosome 6. This same light chain was found by isoelectric focussing to correspond to IgK-Ef1a, another V kappa genetic marker of C.C58 and C.AKR. Isoelectric focussing of approximately 200 C.C58 and C.AKR myeloma light chains revealed three additional C.C58 and four C.AKR light chains that corresponded to IgK-Ef1a-specific light chains. All three additional C.C58 light chains belonged to the V kappa (Ser) group and contained the IB-peptide marker. Thus, the differences in V kappa repertoires represented by the IB-peptide and IgK-Ef1a markers and controlled by genes on chromosome 6 appear to reflect expression (or failure of expression) of a distinct group of V kappa regions.

Amino Acid Sequence↗

A major group of mouse kappa chains controlled by the chromosome 6 locus, IgK-Ef2.

We previously demonstrated that loci closely linked to the Ly-3 locus control the expression of distinct sets of light chains in normal mouse serum immunoglobulin. One of these loci, IgK-Ef2, was shown to control two major bands in normal light chain isoelectric focusing (IF) profiles. Strains possessing the marker bands were designated IgK-Ef2a. Screening of myeloma proteins from the strains BALB/c (IgK-Ef2a) and NZB (IgK-Ef2b) led to the identification of eight proteins in the BALB/c collection having light chains that cofocus precisely with the polymorphic IF bands observed in normal serum light chains. Partial sequence analysis of 3 of the light chains has shown that they are all identical in the first 30 positions, which indicates that they constitute a single variable region of the kappa light chain (VK) group (VK1). The frequency of occurrence of the group within the BALB/c myeloma collections (8 out of 277) suggests that the number of such groups may be closer to 50 than to 100. The finding supports an interpretation of the genetic polymorphism as being in part a result of the absence of genes related to VK1 in IgK-Ef2b strains of mice.

Amino Acid Sequence↗

Antibody gene linkage studies in (NZB X C58) recombinant-inbred lines.

A set of recombinant inbred mouse strains has been constructed from the cross of NZB by C58. These strains provide new tools for the analysis of antibody heavy and light chain genes and NZB autoimmunity. Typing of heavy chain genes confirmed the allotype linkage of the dextran response locus Igh-Dex. One strain has fixed a recombinant chromosome carrying NZB allotype genes and the Dex+ variable region gene from C58. Two kappa-light chain variable region genes, Igk-Pc and Igk-Ef1, co-segregated with the Lyt-2 lymphocyte alloantigen locus. This confirms the tight linkage of these loci and decreases the maximum estimate of the recombination frequency between them to 1.7%.

Animals↗

Ef2: a new LY-3-linked light-chain marker expressed in normal mouse serum immunoglobulin.

A new light-chain marker has been detected in normal mouse serum immunoglobulin light chains by gel isoelectric focusing. The marker (Ef2) involves the presence of two major and several minor bands in the normal light-chain IF profiles. Strains expressing the marker IF bands are designated Igk-Ef2a, whereas those lacking the bands are Igk-Ef2b. The majority of inbred strains are Igk-Ef2a. Strains found to be Igk-Ef2b are NZB/BlNJ, BDP/J, C58/J, I/LnJ, CE/J, and P/J. The strain distribution of the alleles differs from the distribution of alleles at the Ly-2 and Ly-3 loci, suggesting the new marker may represent a separate locus. Genetic studies have shown that Igk-Ef2 locus is closely linked to Igk-Ef1 and Hd loci on Chromosome 6, indicating that it is also closely linked to Ly-3. The relative importance of the bands controlled by the Igk-Ef2 locus suggests that the entire normal light-chain pool could be controlled by as few as 100 such loci.

Alleles↗

Evidence for close linkage of a mouse light chain marker with the Ly-2,3 locus.

Light chains associated with normal serum immunoglobulin can be resolved into a finite number of discrete focusing bands by isoelectric focusing. Four distinct light chain patterns can be distinguished among the inbred mouse strains. In the present studies inheritance of the characteristic light chain patterns has been studied in the AKXL recombinant inbred lines (derived from C57L/J and AKR/J parental lines) and in the inbred Ly-2a,3a congenic line B6.PL-Ly-2aLy-3a/Cy as well as in individual backcross animals of an incipient Ly-2a,3a congenic strain. Virtually complete concordance was observed for the expression of light chains characteristic of phenotype B (AKR-J-like) and the expression of the Ly-2a,3a allele. This observation indicates that a locus controlling light chain structure and/or expression is closely linked (less than 2.6 map units) to the Ly-2,3 locus on mouse Chromosome 6. The locus controlling normal light chain IF-patterns has been designated Ef1.

Animals↗