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D Davidson

Publications and source records attributed to D Davidson.

At least 109 records · Page 6Linked to original sources
PubMed1994

Two distinct protein isoforms are encoded by ntk, a csk-related tyrosine protein kinase gene.

Recently, we and others have cloned cDNAs encoding a second member of the Csk family of inhibitory tyrosine protein kinases, which we have termed Ntk. Intriguingly, the mouse ntk cDNA sequences published by two independent groups differed by the presence or absence of a 136 nucleotide-insert near their 5' ends. In this report, we demonstrate that this 136 nucleotide-sequence likely corresponds to a complete exon in the ntk gene (termed exon 2), and that the two types of cDNAs/transcripts are produced by alternative splicing. Using ribonuclease protection assays, it was also established that brain and lymphoid organs, as well as most hemopoietic cells, predominantly expressed ntk transcripts lacking exon 2. In contrast, selected hemopoietic cell lines, such as the immature myeloid cell lines 32D cl3(G) and WEHI-3B, exclusively possessed exon 2-bearing RNAs. Interestingly, exon 2 introduced a novel in-frame upstream AUG in the ntk transcript, which is in the appropriate context for translation initiation. Evidence was obtained that this AUG is utilized in vivo, and that it extends the amino-terminal sequence of Ntk by 40 amino acids. Indeed, while exon 2-deficient ntk RNAs were translated into a 52 kilodalton (kDa) polypeptide (p52ntk), those bearing exon 2 produced a 56 kDa protein (p56ntk). Furthermore, p56ntk, but not p52ntk, was recognized by an antiserum directed against the novel amino-terminal sequence encoded by exon 2. Additional biochemical characterizations showed that p52ntk and p56ntk were localized to the cytoplasm, and that they partially accumulated in the detergent-insoluble cellular fraction. This last finding suggested that the Ntk proteins can associate with the cytoskeleton. Finally, through linkage analysis of two multilocus crosses, the ntk gene was mapped to Chromosome 10 in the mouse. Taken together, these data showed that ntk, a csk-related tyrosine protein kinase gene, encodes two protein isoforms expressed in distinct cell types. Moreover, they raised the possibility that Ntk may be involved in the regulation of Src-like enzymes in detergent-insoluble cellular compartments.

3T3 Cells↗
PubMed1993

Negative regulation of T-cell receptor signalling by tyrosine protein kinase p50csk.

Tyrosine protein phosphorylation is necessary for antigen receptor-mediated activation of T lymphocytes. This signal is generated at least in part by the Src-related tyrosine protein kinases p56lck and p59fynT (refs 2, 3). The activity of these two enzymes is repressed by phosphorylation of a conserved carboxy-terminal tyrosine residue. Recent studies suggest that this inhibitory phosphorylation may be caused by p50csk (for C-terminal Src kinase), a tyrosine protein kinase which accumulates most abundantly in thymus and spleen. To investigate the function of Csk in T lymphocytes and characterize the processes regulating T-cell receptor (TCR) signalling, we examined the effects of overexpression of Csk on the physiology of an antigen-specific mouse T-cell line. We report here that p50csk negatively regulates TCR-induced tyrosine protein phosphorylation and lymphokine production. This provides evidence for the involvement of Csk in the regulation of T-cell activation.

Animals↗
PubMed1993

Shared sacrifice: the right message for America.

Is President Clinton naive to ask Americans to buy into "shared sacrifice"? Actually, shared sacrifice seems the right message for America in the 1990s, writes Dick Davidson, president of the AHA. In fact, he says, it's probably the only way we'll be able to repair our economy and our health care system.

Community-Institutional Relations↗
PubMed1993

Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus.

The mouse Small eye (Sey) locus is situated on chromosome 2. Molecular analyses have shown that SeyNeu represents a point mutation leading to a splice site error and loss of the functional gene product. The Sey locus has been shown to be identical with the paired box (Pax)-6 gene, which contains paired-like and homoeobox domains and is a developmental control gene. Pax-6 expression occurs in many parts of the central nervous system during embryogenesis. Therefore, we may expect the Sey mutation to result in abnormal development of the central nervous system. The present study shows that Pax-6 mutation has a bimodal effect upon neurogenesis in mouse: it causes a delay of premigratory neurons in a stage-, region-, and gene-dose-dependent manner. Additionally, Sey mutation impairs axonal growth and differentiation. Neurons of the cortical plate cease differentiation on approximately day 16 of gestation and appear to have increased cohesion: their cytoplasm is swollen and vacuolated. These changes coincide both with reduced formation of axons and with the onset of vacuolar degeneration in existing axons, glial cells and radial glial fibers. Consequently, there is an impairment of the peripheral migration of putative neurons so that the neonatal lesion pattern of the neocortical roof becomes dominated by a broad spectrum of neuronal migration disorders.

Animals↗
PubMed1993

Fine-needle aspiration biopsy in oral and maxillofacial surgery.

Fine-needle aspiration biopsy is a technique that is gaining great popularity in both surgical and nonsurgical specialties. Its accuracy, safety, and usefulness have been demonstrated repeatedly; however, its usefulness seems to have been overlooked by oral and maxillofacial surgeons. This technique has many advantages in the diagnosis of mass lesions, including ease of use, cost effectiveness, convenience, and accuracy. It lends itself well to oral and maxillofacial surgery.

Adolescent↗
PubMed1993

Use of artificial sphincter to bowel segment using rectus muscle interposition.

The use of artificial urinary sphincter around the urethra or bladder neck for the management of urinary incontinence secondary to intrinsic urethral sphincter deficiency is now well accepted. However, its use around the bowel to serve as a sphincter in urinary pouches is still anecdotal. Its use in experimental models has been met with failure because of ischemic bowel necrosis at the cuff site. To obviate these difficulties, a new technique was devised using a flap of rectus muscle that acted as a cushion between the cuff and the bowel wall. Results in five dogs showed that bowel wall ischemia is avoided with cuff pressure of 51-60 cm applied constantly for four weeks while providing pressure to leak around the closed cuff with a pressure of 62-75 cm water. Further study is needed to confirm the long-term effect of this technique on the bowel wall and the ability of the sphincter to maintain continence.

Abdominal Muscles↗
PubMed1993

Maternally transmitted partial direct tandem duplication of mitochondrial DNA associated with diabetes mellitus.

Mitochondrial DNA from a 38 year old male with diabetes mellitus and features of mitochondrial dysfunction was analysed and shown to include a population with a partial duplication. The partially duplicated mitochondrial DNA molecules were evident in both muscle and blood. The region of mitochondrial DNA duplicated includes the origin of heavy strand replication, but not the light strand origin. This patient has features in common with other cases of partial direct tandem duplications and with a family which was reported to harbour a 10.4 kb mtDNA deletion. Initial restriction enzyme analysis of our case produced results consistent with a partial deletion of mitochondrial DNA. This leads us to propose that the rarity of reports of partial mitochondrial DNA duplications may stem in part from the classification of such mutants as partial deletions.

Adult↗