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T G Parslow

Publications and source records attributed to T G Parslow.

47 records · Page 3Linked to original sources

The immunoglobulin octanucleotide: independent activity and selective interaction with enhancers.

The thymidine kinase (tk) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer, tk promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present, tk promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.

DNA, Viral↗

Gene rearrangements in lymphoma. Applications to dermatopathology.

Clonality is regarded as an important diagnostic feature of B-cell lymphomas, but until recently the clonality of T-cell proliferations could not be directly determined. Elucidation of the genetic events in lymphocytic differentiation has led to the development of an assay for clonality in both B- and T-cell infiltrates. Clonal rearrangement of the immunoglobulin or T-cell receptor genes can be detected by the Southern blot technique. Such rearrangements provide evidence of clonal proliferation, which, in the proper context, can be regarded as a sign of malignancy. The presence of gene rearrangements in poorly differentiated neoplasms may serve as evidence of hematopoietic differentiation, and the pattern of such rearrangements may point to either T- or B-cell lineage. Specific applications to dermatopathology include the evaluation of skin biopsy specimens for cutaneous lymphoma, evaluation of peripheral blood specimens for detection of Sézary's syndrome, and evaluation of lymph nodes and blood for the staging of mycosis fungoides.

B-Lymphocytes↗

Granulomatous slack skin: clonal rearrangement of the T-cell receptor beta gene is evidence for the lymphoproliferative nature of a cutaneous elastolytic disorder.

Granulomatous slack skin (GSS) is characterized by the slow evolution of bulky, erythematous skin folds that have a granulomatous histology, and show destruction of dermal elastic tissue. Several cases have been putatively associated with Hodgkin's disease, and histologic similarities to mycosis fungoides have also been noted. We examined tissue from 3 cases of GSS to determine whether the condition was inflammatory or lymphoproliferative in nature. We found an abnormal, monomorphous T-helper cell immunophenotype, and in all 3 cases, clonal rearrangement of the T-cell receptor beta gene. We conclude that GSS is an indolent cutaneous T-cell lymphoma associated with granulomatous inflammation that mediates elastolysis, producing a distinctive clinical appearance.

Female↗

Hair matrix differentiation. Occurrence in lesions other than pilomatricoma.

The formation of structures resembling hair matrices is the least common form of follicular differentiation and only occurs with any frequency in pilomatricoma. Rarely, follicular cysts and both benign and malignant adnexal tumors can show areas of pilomatricoma-like change, or hair matrix differentiation. Examples of focal hair matrix differentiation in a follicular cyst, a cutaneous mixed tumor, and an adnexal carcinoma are presented. Each of these cases also demonstrates the presence of limited differentiation toward structures of the inner root sheath.

Adult↗

Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence.

Recent investigations have suggested that tissue-specific regulatory factors are required for immunoglobulin gene transcription. Cells of the mouse lymphocytoid pre-B-cell line 70Z/3 contain a constitutively rearranged immunoglobulin kappa light chain gene; the nucleotide sequence of this gene exhibits all the known properties of a functionally competent transcription unit. Nevertheless, transcripts derived from this gene are detectable only after exposure of the cells to bacterial lipopolysaccharide, implying that accurate DNA rearrangement is not sufficient to activate expression of the gene. Comparison of the sequence of the 70Z/3 kappa light chain gene with those encoding other immunoglobulin heavy and light chains has revealed that a distinctive promoter region structure is characteristic of this multigene family. The sequence A-T-T-T-G-C-A-T lies approximately 70 base pairs upstream from the site of transcriptional initiation in every light chain gene examined; in heavy chain genes, the corresponding location is occupied by the precise inverse (A-T-G-C-A-A-A-T) of this sequence. Although adjacent regions of DNA have diverged extensively in evolution, these octanucleotide sequences are stringently conserved at this location among diverse immunoglobulin genes from at least two mammalian species. The proximity of this conserved octanucleotide block to the site of transcriptional initiation suggests that it may serve as a recognition locus for factors regulating immunoglobulin gene expression in a tissue-specific fashion.

Animals↗

Idiotype-specific T cell suppression of light chain mRNA expression in MOPC-315 cells is accompanied by a posttranscriptional inhibition of heavy chain expression.

Earlier studies have shown that idiotype-specific T suppressor cells can directly inhibit the biosynthesis and subsequent secretion of immunoglobulin from the BALB/c myeloma, MOPC-315. This suppression is highly specific and does not affect nonimmunoglobulin protein synthesis in these cells. The selective character of this suppression suggested a transcriptional or translational mechanism of control. Therefore, we analyzed suppressed MOPC-315 cells for the expression of light and heavy chain mRNAs. Since the events that occur in a B cell subsequent to reception of suppressive signals from T cells are presently unknown, these experiments address a fundamental aspect of B cell regulation. Another important aspect of these studies is that they deal with a suppressor T cell that clearly operates directly upon the antibody-secreting cell. This system involves regulation of a B cell differentiative function without influencing the B cell clonal size. We have employed the trinitrophenyl (TNP)-specific myeloma, MOPC-315, because it provides a source of monoclonal B cells which in earlier studies have been shown to be responsive to idiotype-specific and TNP-antigen-specific immunoregulatory signals. The idiotype-specific T cells were generated by hyperimmunizing BALB/c mice with the myeloma protein bearing the 315 idiotype, in complete Freund's adjuvant. Poly A+ mRNA was isolated from MOPC-315 cells following coculture with either normal or idiotype-immune T cells. The mRNA was analyzed using hybridization techniques and cDNA probes specific for alpha or lambda 2 light chain constant regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Structure of a nuclease-sensitive region inside the immunoglobin kappa gene: evidence for a role in gene regulation.

A discrete chromatin region inside the active immunoglobulin kappa gene is preferentially accessible to cleavage by nucleolytic enzymes. This region comprises 200-250 bp of DNA, and is situated within the large intron of the gene, approximately 600 bp upstream from the constant region coding sequence. The local chromatin structure of this region correlates with tissue-specific kappa gene expression: it is resistant to nucleolytic digestion in the inactive kappa genes of murine brain and liver nuclei, but becomes uniquely sensitive to cleavage by deoxyribonuclease I or by a variety of restriction endonucleases in the chromatin of kappa-producing cells. Nuclease sensitivity at this site occurs in both rearranged and unrearranged kappa alleles, and can be maintained in the absence of ongoing kappa transcription. The nucleotide sequence of the hypersensitive region has been selectively conserved in evolution, and includes both a 7 bp inverted repeat sequence and a short segment homologous to the transcriptional enhancer elements of certain eukaryotic viruses. Molecular events occurring at this locus may play a role in the regulation of kappa gene expression, perhaps by influencing the activity of promoter sequences several kilobases upstream.

Alleles↗

Suppressor T cell action inhibits the expression of an excluded immunoglobulin gene.

Cells of the murine plasmacytoid line MOPC-315 synthesize two distinct immunoglobulin light chains: a normal lambda II protein, which is incorporated into secretory and surface-bound immunoglobulin, and a truncated, nonfunctional lambda I protein found only in the cytoplasm. Idiotype-specific suppressor T lymphocytes selectively inhibit the expression of both lambda II- and lambda I-specific messenger RNA by MOPC-315 cells. This finding demonstrates that phenotypically excluded light chain genes can be subject to immunoregulatory control and suggests that the expression of divergent lambda isotypes may be coordinately regulated in immunoglobulin-secreting cells.

Animals↗