PubMed Health⌕ Search

Biomedical subjects

M L Richards

Publications and source records attributed to M L Richards.

8 recordsLinked to original sources
PubMed1991

Complete genomic sequence of the murine low affinity Fc receptor for IgE. Demonstration of alternative transcripts and conserved sequence elements.

The complete sequence of the murine low affinity Fc receptor for IgE (Fc epsilon RII), including the 5' and 3' flanking sequences, is reported. The murine Fc epsilon RII gene spans 12.9 kb and includes 12 exons surrounding 11 introns. The composite exon sequence is virtually identical to previously reported murine Fc epsilon RII cDNA sequences. Much of the proximal promoter regions of the mouse and human homologues of Fc epsilon RII show remarkable homology to each other, including three promoter elements previously identified for MHC class II genes. The reported exon/intron structure of the human FC epsilon RII is similar to the murine homologue, except that the latter has an additional exon coding for a fourth amino acid repetitive sequence (vs three in the human gene). RNase protection studies have identified an additional transcript within intron 2 of murine Fc epsilon RIIa, similar to the human Fc epsilon RIIb form but with a different predicted sequence of the first six amino acids. This transcript is present in the mRNA of purified splenic B cells, but not in the mRNA of the Fc epsilon RII+ B lymphoma cell line M12.4.5. The murine Fc epsilon RII gene contains a large intron (4.2 kb) separating the lectin and nonlectin coding regions, and several repetitive sequences are found clustered within this intron. These results emphasize the importance of the demarcation between these domains and allude to their evolutionary and functional significance.

Amino Acid Sequence↗
PubMed1991

mRNA variants encoding multiple forms of the high-affinity IgE receptor alpha subunit in transformed and nontransformed mast cells.

Multiple mRNA species encoding several predicted forms of the high-affinity IgE receptor alpha subunit (Fc epsilon RI-alpha) have been previously characterized from rat basophilic leukemia cells. Using the polymerase chain reaction procedure, we have extended these findings to show that one Fc epsilon RI-alpha mRNA variant, characterized by a 163-bp deletion within the coding sequence, exists in normal rat connective tissue mast cells as well as in both transformed and non transformed murine mast cell lines. In addition, a partial murine Fc epsilon RI-alpha genomic clone, spanning the internal-deletion sequence, has been identified, and from analysis of this sequence a mechanism of alternative pre-mRNA splicing is proposed. Finally, mRNA variants have been translated in a cell-free system and the protein products partially characterized.

Amino Acid Sequence↗
PubMed1991

Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23).

Recent studies have established that the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) is a structurally and functionally unique immunoglobulin receptor. DNA sequence analysis predicts that, in contrast to other FcR, Fc epsilon RII is not a member of the immunoglobulin gene superfamily and, indeed, is inserted into the membrane in opposite orientation from most other membrane proteins. While the Fc epsilon RII of macrophages, eosinophils, and platelets mediate IgE-dependent cytotoxicity and promote phagocytosis of IgE-antigen complexes, the function of Fc epsilon RII on B lymphocytes remains unclear. Much effort has been directed toward establishment of its role in IgE regulation, but the plurality of B cell Fc epsilon RII expression, i.e. greater than 90% of the mu + /delta + B lymphocytes, is incongruous with simply a role in regulating only IgE responses. Hence, the discovery that Fc epsilon RII is identical to the B-cell activation antigen, CD23, together with its novel structural features, suggests an additional more important role for this interesting protein and would explain the disparity between a commonly expressed receptor with apparently limited functions.

Antigens, CD↗
PubMed1990

The binding of IgE to murine Fc epsilon RII is calcium-dependent but not inhibited by carbohydrate.

Despite extensive study, little is known about the functions of the moderate affinity IgE receptors (Fc epsilon RII) on B cells. Recent cDNA and genomic cloning studies have demonstrated that, in contrast to other FcR, Fc epsilon RII is not a member of the Ig gene superfamily. Moreover, it uniquely expresses a region that is highly homologous with a membrane-associated, calcium-dependent binding lectin, the asialoglycoprotein receptor. We now report that the interaction between IgE and the Fc epsilon RII of murine B cells and macrophages requires calcium. Furthermore, as might be expected of asialoglycoprotein lectins, this binding was pH-dependent and resulted in ligand internalization. However, although 125I-Fc epsilon RII bound in a calcium-dependent manner to monosaccharide-agarose beads, high concentrations of mono- and disaccharides did not inhibit the interaction between either 125I-IgE and intact B cells or 125I-Fc epsilon RII (from surface-labeled B cells) and IgE-Sepharose. These results suggest that although murine Fc epsilon RII is a lectin, it is not strictly dependent upon IgE oligosaccharides for its binding to IgE.

Animals↗
PubMed1990

The induction of murine B cell Ia by IgE-antigen complexes is dependent on protein synthesis and preceded by class II mRNA accumulation.

Complexes of murine monoclonal anti-DNP IgE and DNP-OVA interact with murine B cells to stimulate expression of cell surface Ia antigens. Enhanced membrane expression of class II MHC antigens was accompanied by a threefold increase of I-A and I-E transcripts, as measured by Northern blot. Peak accumulation of Ia mRNA were detected after 6 hr of incubation with IgE-antigen complexes and returned to control levels after 12 hr of incubation. Hence, induction of Ia mRNA by IgE-antigen complexes was compatible with cell surface Ia expression, both quantitatively and with regard to the time frame. The Ia-inductive effects of both IL-4 and IgE-antigen complexes were inhibited by cycloheximide and actinomycin-D. However, whereas actinomycin-D and cycloheximide blocked IL-4 induction of Fc epsilon RII expression, inhibition of transcription or protein synthesis did not abrogate the increased expression of Fc epsilon R associated with IgE-antigen complexes. These results suggest that the IgE-antigen-induction of B cell Ia expression follows from activation of transcription and de novo synthesis of Ia antigens.

Animals↗
PubMedDate not supplied

Cigarette smoking and atherosclerosis in autopsied men.

The association of cigarette smoking and atherosclerorosis was investigated in 1320 autopsied men, 25--64 years of age. Aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. Data were analysed for black and white men in the total sample of cases and also in groups according to the presence (selected disease group) or absence (basal group) of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diabetes, stroke, etc.). Atherosclerotic involvement of aorta and coronary arteries was greatest in heavy smokers and least in nonsmokers for both races in the total sample of cases, the basal group and the selected disease group.

Adult↗
PubMedDate not supplied

Individual cigarette usage: self-reported data as a function of respondent-reported data.

The interview method was used to collect data from living respondent-subject pairs regarding cigarette usage of the subject; the nonsmoker subject was explicitly not studied. Several different measures of usage were tested. The mean correlation coefficient between subject-reported data and the corresponding respondent-reported data was 0.86; that is, at least 70% of the variability in subject-reported data can be accounted for from information obtained from an appropriate living respondent closely associated with the subject. Selected regression equations are presented for estimating cigarette usage of a subject from data provided by a respondent.

Adolescent↗