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Biomedical subjects

R Wall

Publications and source records attributed to R Wall.

At least 163 records · Page 9Linked to original sources
PubMed1983

The structure of the mouse immunoglobulin in gamma 3 membrane gene segment.

The genomic region containing the mouse immunoglobulin gamma 3 heavy chain membrane (M) exons has been located and sequenced. The exon structure is highly similar to that of the other mouse gamma chains, with strong sequence conservation in the coding regions and the intron 5' to the M1 exon. The intron between M1 and M2 shows moderate sequence homology but very strong conservation of size. RNA blots suggest that gamma 3 membrane exon usage is similar to that seen in other immunoglobulin membrane heavy chain mRNAs. The transmembrane region contains the invariant residues which have been noted in all other heavy chain sequences and which were previously proposed to be interactive in a two-chain model for insertion through the lymphocyte membrane. Conserved residues with similar spacing have been seen in class II histocompatibility antigens, which are also two-chain transmembrane molecules, but not in class I antigens, which span cell membranes with a single chain.

Amino Acid Sequence↗
PubMed1983

Human-human B cell hybridomas from in vitro stimulated lymphocytes of patients with common variable immunodeficiency.

Human-human B cell hybridomas have been established from the peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) by fusion with an HGPRT-negative B lymphoblastoid cell line. IgM-secreting hybridomas were successfully obtained from CVI lymphocytes after stimulation for 5 days in vitro with a combination of PWM and Staphylococcus aureus strain Cowan I. Fusion of peripheral blood lymphocytes that were stimulated for 5 days in vitro with a single mitogen resulted in no viable hybrids from a total of 600 X 10(6) CVI lymphocytes. The combination of PWM and Cowan I did not induce appreciable Ig secretion from the CVI lymphocytes during the 5-day course, although it did so in normal lymphocytes. After the 5-day stimulation with this mitogen combination, however, a large percentage of the original number of peripheral blood cells were recovered, and these had a fusion frequency of approximately 1 to 2 per 10(6) with the B lymphoblastoid line. Fifteen cloned IgM-secreting hybridomas have been isolated from five different CVI patients. These hybridomas are tetraploid and have been stable in culture for 6 to 12 mo. All of the hybridoma lines that were examined contain a functionally rearranged IgM heavy chain gene from the B cell parent of the CVI patients. These human-human B cell hybridoma lines will enable a more thorough characterization of the B cell defects involved in CVI at the cellular and molecular levels.

Adult↗
PubMed1983

Primary adrenal insufficiency manifesting as malignant lymphoma.

Primary adrenal insufficiency associated with a hematologic malignant neoplasm is a rare entity. Most malignant neoplasms with metastases to the adrenal gland are secondary to solid carcinomas of the lung and breast. A 55-year-old man was seen with clinical and biochemical evidence of primary adrenal insufficiency as the initial manifestation of his malignant lymphoma. At autopsy the architecture of both adrenal glands was completely effaced by malignant plasmacytoid cells. This case emphasizes that infiltrative lymphoma of the abdomen is a rare cause of primary adrenal insufficiency and may be the initial manifestation. Furthermore, it should be included in the differential diagnosis.

Adrenal Gland Diseases↗
PubMed1983

Naval aviation mishaps and fatigue.

Naval aircraft mishap data were analyzed to determine if statistical relationships among variables generally associated with fatigue and mishap liability exist. Pilots in mishaps were divided into two groups: those who were causally involved and those who were not. The results demonstrated that fighter and helicopter pilots who had worked at least 10 h in the previous 24 were significantly more likely to fall in the causally involved group. Variables related to sleep, continuous duty, missions performed, and hours flown in the immediate past, however, showed no significant relationships with mishap liability. Analysis of mishap rates as a function of time of departure, however, indicated that rates tended to be lowest for flights originating between 0900 and 1800, a result that possibly supports the hypothesis that "circadian desynchronization" contributes to mishaps.

Accidents, Aviation↗
PubMed1982

Antiarsonate antibody response: a model for studying antibody diversity.

The use of two polyclonal activators, dextran sulfate (DxS) and lipopolysaccharide (LPS), with or without the presence of additional antigen, is presented here as a system for exploring the antibody response of normal (naive) amd primed B cells. This system expands populations of cells not normally observed under in vivo regulation. By fusing such unnaturally activated B cells, anti-p-azophenylarsonate hybrids were produced that secrete different isotypes of antibodies. The frequencies of isotopes expressed by these hybrids may correspond to the chromosomal order of the heavy chain genes because greater numbers of IgM- and IgG3-secreting hybrids were produced than IgG2a hybrids. Only one IgA hybrid was observed. When DxS and LPS were used to stimulate antigen-primed B cells, hybrids were generated that simultaneously secrete two isotopes of antibody. These hybrids may represent a model of the antigen-stimulated maturational class-switch step observed in normal B cells that involves the expression of IgM and IgG isotypes by the same cell. Such hybrids offer an opportunity to study antibody regulation and diversity by examining the rearrangement of genes during the Ig switch, by exploring the nature of the necessary transitions of mRNA transcription and translation to produce functional antibodies, and by probing the structure and specificity of such antibodies.

Animals↗
PubMed1981

Gene segments encoding transmembrane carboxyl termini of immunoglobulin gamma chains.

In cell lines producing IgM, secreted and membrane bound forms of immunoglobulin mu heavy chains are produced from two separate mu mRNAs that are identical except for alternative 3' coding sequences. We now show that cell lines producing IgG likewise contain two mRNA species for immunoglobulin gamma chains. The major, 1.7 kilobase (kb) species encodes secreted gamma chains. A less abundant species of 3-4 appears to encode membrane bound gamma chains, in that it contains an alternative 3' end encoded in separate exons 3' to the remainder of the gene. The first exon of this M gene segment has been identified in chromosomal gamma 1 and gamma 2b gene clones by its sequence homology with the corresponding exon in the mu gene. Like the mu M exon, it encodes a probable transmembrane polypeptide segment. The flanking DNA sequences show a patchwork pattern of homology between genes that suggests a checkered evolutionary history.

Amino Acid Sequence↗
PubMed1981

Immunoglobulin heavy chain genes: demethylation accompanies class switching.

The methylation of immunoglobulin heavy chain genes was examined before and after class switching, by using the Hpa II/Msp I restriction mapping technique. The mu, delta, and gamma 1 genes all are methylated in cells that do not express them but are demethylated when they are expressed. In particular, the delta gene remains methylated, and thus presumably untranscribed, in a cell line that probably represents an early stage of B-cell differentiation and produces only mu heavy chains. Because mu and delta RNAs are cotranscribed from a single complex transcription unit at a later stage of B-cell differentiation, this finding implies that the mu-plus-delta complex transcription unit is of variable length.

5-Methylcytosine↗
PubMed1981

Expression of IgD may use both DNA rearrangement and RNA splicing mechanisms.

From a library of mouse sperm DNA, we have isolated two overlapping clones which contain the C(delta) gene. One of these clones also contains the C(mu) gene. The C(delta) gene is separated from the C(mu) membrane exons by approximately 2 kilobases (kb) of DAN. The C(delta) gene was identified by (a) hybridization to poly(A)(+)RNA prepared from the IgD-producing rat plasma cell tumor IR731, and (b) homology of a translated nucleotide sequence to the amino acid sequence of the human delta chain. The C(delta) gene spans 8 kb of DNA in the germ line. Plasmid subclones of the C(delta) gene were used as probes in Southern and RNA blot experiments. RNA blot analysis of cytoplasmic poly(A)(+)RNA from IR731 and a mu(+)delta(+) B-cell hybridoma revealed 1.6- and 2.7-kb delta mRNA species with different 3' ends, which presumably encode the secreted and membrane-bound forms, respectively, of the delta chain. Southern blot analysis of DNA from two mu(+)delta(+) lymphomas revealed that the C(delta) gene is in the germ-line configuration in each case. Restriction map analysis of C(mu) and C(delta) genomic clones isolated from a library of normal mu(+)delta(+) B-cell DNA also gave no evidence for DNA rearrangement in the region between the C(mu) and C(delta) genes. Taken together, these data suggest that IgD expression in mu(+)delta(+) B cells does not involve a V(H)-to-C(delta) DNA switch rearrangement. We propose that simultaneous expression of C(delta) and C(delta) with a single V(H) gene is mediated by two alternative routes of RNA processing of a primary nuclear transcript which contains the V(H), C(mu), and C(delta) genes. In contrast, analogous experiments with myeloma IR731 DNA revealed that the C(mu) gene has been deleted from the myeloma DNA and that the C(delta) gene has undergone DNA rearrangement, presumably including a switch recombination of the V(H) gene from the C(mu) to the C(delta) gene. These results indicate that two alternative mechanisms may be used in the expression of IgD molecules-RNA splicing in B cells and DNA rearrangement in plasma cells.

Animals↗
PubMed1981

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Demography↗
PubMed1980

RNA splicing generates a variant light chain from an aberrantly rearranged kappa gene.

Both C kappa regions in MPC 11 cells are rearranged into active transcripion units, one producing a normal kappa chain and the other an internally deleted kappa fragment lacking a V region. The gene coding for the kappa fragment mRNA is aberrantly rearranged and lacks a site for V leads to C kappa splicing. An alternative splicing event which deletes the V region from the nuclear RNA precursor generates the kappa fragment mRNA.

Animals↗