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Biomedical subjects

K A Zimmerman

Publications and source records attributed to K A Zimmerman.

8 recordsLinked to original sources
PubMed1988

Gene expression in renal growth and regrowth.

To elucidate the molecular events associated with postnatal and compensatory renal growth, the expression of growth/differentiation genes (c-fos, c-myc, c-H-ras, c-K-ras), a stress-related gene (HSP70) and a structural gene (collagen type IV, alpha 1 and 2) were examined. Northern analysis of messenger ribonucleic acid from the newborn mouse reveals high levels of expression of HSP70, c-H-ras, and c-K-ras during the first week of life. By day 40 HSP70-related and c-H-ras expression decreases somewhat, c-K-ras remains unchanged and collagen type IV, which encodes for the renal glomerular basement membrane, expression decreases significantly. During compensatory renal growth increased expression of HSP70, c-H-ras and c-K-ras occurs. The results seem to indicate that growth/differentiation genes may be necessary for continued cell growth (hypertrophy) in postnatal and compensatory renal growth, and that collagen type IV formation continues up through week 2 of postnatal growth consistent with the interval of glomerular basement membrane formation.

Animals↗
PubMed1987

Structure and expression of the human and mouse T4 genes.

The T4 molecule may serve as a T-cell receptor recognizing molecules on the surface of specific target cells and also serves as the receptor for the human immunodeficiency virus. To define the mechanisms of interaction of T4 with the surface of antigen-presenting cells as well as with human immunodeficiency virus, we have further analyzed the sequence, structure, and expression of the human and mouse T4 genes. T4 consists of an extracellular segment comprised of a leader sequence followed by four tandem variable-joining (VJ)-like domains, a transmembrane domain, and a cytoplasmic segment. The structural domains of the T4 protein deduced from amino acid sequence are precisely reflected in the intron-exon organization of the gene. Analysis of the expression of the T4 gene indicates that T4 RNA is expressed not only in T lymphocytes, but in B cells, macrophages, and granulocytes. T4 is also expressed in a developmentally regulated manner in specific regions of the brain. It is, therefore, possible that T4 plays a more general role in mediating cell recognition events that are not restricted to the cellular immune response.

Amino Acid Sequence↗
PubMed1986

Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching.

We describe rearrangement events which alter expression from a productive VHDJH rearrangement in an Abelson murine leukemia virus-transformed pre-B cell line. One such rearrangement results in replacement of the initially expressed variable region gene by a site-specific join between the open reading frame of a LINE-1 repetitive element and a remaining JH segment. We discuss this event in the context of the 'accessibility' model of recombinase control, and with respect to similar rearrangements involved in oncogene activation. In another subclone of the same pre-B cell line, altered heavy chain expression resulted from a mu to gamma 2b class switch recombination which occurred by a recombination-deletion mechanism but involved a complex inversion. We provide evidence that the germline gamma 2b region is specifically expressed in pre-B cell lines and early in normal development. We propose that the predisposition of pre-B cell lines to switch to gamma 2b production may reflect a normal physiological phenomenon in which the switch event is directed by an increased 'accessibility' of the germline gamma 2b locus to switch-recombination enzymatic machinery. Our findings support the hypothesis that the apparently distinct recombination systems involved in variable region gene assembly and heavy chain class switching are both directed by the accessibility of their substrate gene segments.

Abelson murine leukemia virus↗
PubMed1986

Enhanced expression of the N-myc gene in Wilms' tumors.

Activation of myc-family oncogenes has been implicated in the genesis of a variety of neoplasms. In addition, these genes exhibit specific patterns of expression during murine development. We now report that N- and c-myc are differentially expressed in normal developing human renal tissues and in Wilms' tumor, a neoplasm which derives from primitive kidney cells. Twelve of 13 Wilms' tumors tested exhibited greatly enhanced levels of expression which occurred in the absence of gene amplification. We also detected N-myc expression in other primitive neoplasms including medulloblastoma and hepatoblastoma. Our observations suggest that N-myc expression is not limited to neuroectodermal tumors as was previously thought, but is a marker for several neoplasms that derive from primitive cell precursors. Finally, high level expression of N-myc was associated with markedly diminished levels of c-myc, suggesting that enhanced expression of N-myc gene might lead to down-regulation of c-myc.

Fetus↗
PubMedDate not supplied

Differential expression of myc family genes during murine development.

The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.

Animals↗