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D Davidson

Publications and source records attributed to D Davidson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Interactions of the SH2 domain of lymphocyte-specific tyrosine protein kinase p56lck with phosphotyrosine-containing proteins.

We have previously demonstrated that the non-catalytic Src homology 2 (SH2) domain is required for both positive and negative regulation of the catalytic function of the lymphocyte-specific tyrosine protein kinase p56lck. Indeed, the ability of activated p56lck molecules (tyrosine 505 to phenylalanine 505 mutants) to enhance T-cell receptor (TCR)-induced tyrosine protein phosphorylation is dramatically reduced by deletion of the SH2 domain. Paradoxically, removal of the SH2 sequence also results in constitutive elevation of the catalytic function of wild-type Lck polypeptides, rendering them capable of oncogenic transformation of rodent fibroblasts. As SH2 sequences can mediate binding to phosphotyrosine-containing peptides, the ability of the Lck SH2 domain to interact with tyrosine-phosphorylated proteins was tested. We found that the SH2 sequence of p56lck can bind several of the TCR-regulated tyrosine phosphorylation substrates in vitro. One of the substrates, an 80-kilodalton (kDa) phosphoprotein (p80) showed the tightest binding to the SH2 domain of Lck. Additionally, it was observed that the SH2 domain of Lck can bind a synthetic peptide containing the phosphorylated carboxy-terminal tyrosine 505 of p56lck. Indirect evidence indicating that the SH2 region interacts with the tyrosine-phosphorylated carboxy terminus of Lck in vivo was also obtained. As deletion of the SH2 domain or mutation of tyrosine 505 results in p56lck activation in vivo, it is conceivable that interactions between these two regions impose a conformation that is unfavorable to phosphorylation of intracellular substrates. Collectively, these findings suggest that the SH2 domain modulates the catalytic function of Lck through complex interactions with phosphotyrosine-containing proteins.

Animals↗
PubMed1993

A modest proposal.

Explore the source record for details and available documents.

Health Care Costs↗
PubMed1992

Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn.

Recent observations suggest that the src-related tyrosine protein kinase p59fyn may be involved in antigen-induced T lymphocyte activation. As a result of alternative splicing, p59fyn exists as two isoforms that differ exclusively within a short sequence spanning the end of the Src Homology 2 (SH2) region and the beginning of the tyrosine protein kinase domain. While one p59fyn isoform (fynB) is highly expressed in brain, the alternative product (fynT) is principally found in T lymphocytes. To further understand the role of p59fyn in T cell activation and to test the hypothesis that p59fynT serves a tissue-specific function in T lymphocytes, we have examined the effects of expression of activated versions (tyrosine 528 to phenylalanine 528 mutants) of either form of p59fyn on the physiology of an antigen-specific mouse T cell hybridoma. Our results demonstrated that the two forms of fyn, expressed in equivalent amounts, efficiently enhanced antibody-induced T cell receptor (TCR)-mediated signals. In contrast, only p59fynT increased interleukin 2 production in response to antigen stimulation. This finding implies that the distinct p59fyn isoform expressed in T lymphocytes regulates the coupling of TCR stimulation by antigen/major histocompatibility complex to lymphokine production.

Animals↗
PubMed1992

Src-related protein tyrosine kinases and T-cell receptor signalling.

Upon antigen stimulation, the T-cell receptor for antigen transduces an intracellular protein tyrosine phosphorylation signal that is critical for subsequent T-lymphocyte activation. As the antigen receptor does not possess an intrinsic protein tyrosine kinase activity, the mechanism by which it regulates protein tyrosine phosphorylation is unconventional. Evidence is increasing that the Src-related protein tyrosine kinases P56lck and p59fyn, as well as the protein tyrosine phosphatase CD45, are involved in this process.

Genes, src↗
PubMed1992

Prolonged pulmonary hypertension caused by platelet-activating factor and leukotriene C4 in the rat lung.

Platelet-activating factor (PAF) and leukotrienes (LTs) are potent pulmonary hypertensive and inflammatory mediators produced by the lung. Previously we showed that a rapid injection of PAF into the pulmonary artery of an isolated rat lung produced an extended elevation in mean pulmonary arterial pressure (PAP). The objective of the present study was to determine whether the extended pressor response induced by PAF was caused by prolonged activation of the 5-lipoxygenase pathway or slow clearance of LTs from the lung parenchyma. Rat lungs were perfused with a nonrecirculating physiological salt solution that contained indomethacin and albumin. Five minutes after a rapid injection of PAF into the pulmonary artery catheter, the following elevations (mean % above baseline) were observed: PAP (83%), LTB4 (3,260%), LTC4 (1,490%), LTD4 (970%), and LTE4 (1,500%). At 20 min these levels declined but were still significantly elevated above baseline. The 5-lipoxygenase inhibitor diethylcarbamazine (DEC), administered before the PAF injection, inhibited the elevations of PAP and all LTs. DEC administration that began 5 min after PAF reduced PAP and only LTC4 levels at 20 min in comparison to lungs with no DEC. The 5-lipoxygenase-activating protein inhibitor MK886, administered orally 2-6 h before perfusion, also inhibited the pressor response to PAF as well as LT production, as did DEC. We conclude that 1) the extended pulmonary hypertension induced by PAF was caused mainly by prolonged activation of 5-lipoxygenase with LTC4 production, 2) the relative overall lung clearance of LTB4, LTD4, and LTE4 was slower than that of LTC4, and 3) LTB4, LTD4, and LTE4 had no appreciable pressor effect.

Animals↗
PubMed1992

A national survey of educational preparation programs for early intervention specialists.

To examine the status of preprofessional education in early intervention, we conducted a nationwide survey of college and university programs offering degrees in education of the deaf. Curriculum content and practicum experiences with infants and toddlers and their families were examined, as well as general comments and recommendations of program directors. Additional information was sought from programs offering specializations at the preschool level to determine whether they had CED affiliation, and if so, whether they were certified in the areas of parent-infant education or early childhood education. The findings are discussed in the context of Public Law 99-457 and the growing emphasis on family centered early intervention.

Adult↗
PubMed1992

Simple surgical treatment of nonparasitic hepatic cysts.

Benign nonparasitic liver cysts are uncommon lesions. Incidental diagnosis is increasing with the advent of routine abdominal computed tomography and ultrasound scanning. Cysts that attain massive proportions often become symptomatic and require therapeutic intervention. Surgical resection and Roux-en-Y cystojejunostomy drainage have been the treatments of choice, but simpler unroofing techniques without drainage have recently been employed with success. Three patients with symptomatic, large, nonparasitic cysts were surgically treated in such a fashion without complication and form the basis of this report. The technique of wide unroofing involves excision of the nonhepatic cyst wall with oversewing of communicating biliary radicals. No recurrences have been detected in follow-up screening. Wide unroofing is a simple and yet reliable surgical option for the treatment of symptomatic hepatic cysts.

Aged↗
PubMed1991

Use of exoglycosidases from Mercenaria mercenaria (hard shelled clam) as a tool for structural studies of glycosphingolipids and glycoproteins.

The hepatopancreatic extract of M. mercenaria (hard shelled clam) was found to be a rich source for at least 16 different glycosidases. These glycosidases were successfully employed for the degradation of oligosaccharides, glycolipids, and glycoproteins at analytical as well as preparative levels. The identified glycosidases differ considerably in their stability profiles with respect to time and temperature of storage and presence of glycerol. However, most of the enzymes show higher activity at pH 4.5 than at pH 7.0, and could be bound on a DEAE CL-6B Sepharose anion-exchange column suggesting similar charge characteristics on the protein surface. A Gal beta 1, 3R linkage-specific beta-galactosidase activity has also been detected in the glycosidase-enriched fraction and has been utilized to obtain quantitative conversion of the ganglioside GM1 to GM2 on a preparative scale. The glycosidase-rich extract does not have detectable protease activity at the pH of optimal glycosidase activity (pH 4.5) and, hence, can be safely used for specific hydrolysis of carbohydrate moieties of glycoproteins and glycopeptides. This is the first report to characterize a repertoire of glycosidases from an inexpensive, dependable and convenient source that can be easily employed for compositional studies involving glycoconjugates.

Animals↗
PubMed1991

Blunting of neuroendocrine responses to infusion of L-tryptophan in women with perimenstrual mood change.

The neuroendocrine response to L-tryptophan infusion was measured at two stages of the menstrual cycle, premenstrually and postmenstrually, in 13 women with and 13 women without premenstrual depression (the MC and NMC groups respectively). Previous studies have shown that in non-depressed women, this challenge test results in an increase in circulating prolactin and growth hormone. In depressed women both responses are blunted. In this study the growth hormone and cortisol responses were smaller in the MC group than the NMC group on both occasions. The prolactin response was blunted premenstrually compared with postmenstrually in both groups. These findings suggest that women who experience premenstrual depression may have neuroendocrine abnormalities throughout the cycle. The neurotransmitter abnormalities reflected in these altered endocrine responses appear to interact with neuroendocrine changes that normally occur premenstrually resulting in a vulnerability to depression at that phase of the cycle.

Adolescent↗
PubMed1991

Endothelium-derived relaxing factor: evidence that it regulates pulmonary vascular resistance in the isolated neonatal guinea pig lung.

Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, has been previously identified in the pulmonary and systemic vasculature of the newborn guinea pig using isolated arterial rings. The aim of our study was to determine if EDRF regulates vasomotor tone at the level of resistance vessels in the neonatal pulmonary circulation. Isolated lungs from guinea pigs (1-3 d old, n = 4-8/protocol) were ventilated with room air and perfused with a Krebs-Henseleit solution containing albumin at a constant flow. Angiotensin II (AII, 6 nM) was added to the perfusate to give a stable elevation in mean pulmonary artery pressure (PAP) from 7.0 +/- 1.1 to 19.7 +/- 1.5 torr, a 182 +/- 32% (mean +/- SEM) increase above baseline. Addition of bradykinin (BK, 10 nM) or L-arginine (2 mM) markedly reduced the AII-induced elevation in PAP. At the steady state response to BK (33% above baseline), addition of Hb (10 microM, binds EDRF), NG-monomethyl-L-arginine (NMA, 100 microM, blocks EDRF production), NMA (200 microM), or NMA + Hb, reversed the effect of BK to the following levels of PAP above baseline: 77 +/- 5, 94 +/- 24, 163 +/- 20, or 246 +/- 25%, respectively (p less than 0.05). Indomethacin had no effect on BK-induced vasodilation. In separate studies, NMA (200 microM) increased baseline PAP by 46 +/- 13% and NMA pretreatment raised the AII-pressor response (AII 6 nM) from 133 +/- 49 to 306 +/- 65% above baseline PAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

The lymphocyte-specific tyrosine protein kinase p56lck.

The CD4 and CD8 T cell surface antigens are physically associated with the tyrosine protein kinase p56lck. Accumulating data indicate that p56lck transduces intracellular tyrosine protein phosphorylation signals upon engagement of CD4 and CD8 by major histocompatibility complex (MHC) determinants expressed on antigen-presenting cells (APCs). Recent studies show that these p56lck-related phosphorylation events enhance T cell receptor (TCR)-mediated functions and are critical for the proposed co-receptor roles of CD4 and CD8. p56lck is also capable of enhancing antigen receptor responsiveness in the absence of CD4 or CD8 expression, suggesting that it can directly contribute to the TCR-induced tyrosine phosphorylation signal.

Amino Acid Sequence↗
PubMed1990

The candidate Wilms' tumour gene is involved in genitourinary development.

Wilms' tumour is an embryonic kidney tumour thought to arise through aberrant mesenchymal stem cell differentiation and to result from loss of function of a 'tumour suppressor' gene(s). Both sporadic and syndrome-associated Wilms' tumours are accompanied by an increased frequency of abnormalities of the urinary tract and genitalia. Deletional analysis of individuals with the WAGR syndrome (for, Wilms' tumour, aniridia, genitourinary abnormalities and mental retardation) showed that a Wilms' tumour gene lies at chromosomal position 11p13. This led to the isolation of a candidate Wilms' tumour gene, encoding a zinc-finger protein which is likely to be a transcription factor. To gain insight into the role of this candidate gene in normal development and tumorigenesis, we have now performed in situ messenger RNA hybridization on sections of human embryos and Wilms' tumours. The candidate Wilms' tumour gene is expressed specifically in the condensed mesenchyme, renal vesicle and glomerular epithelium of the developing kidney, in the related mesonephric glomeruli and in cells approximating these structures in tumours. The other main sites of expression are the genital ridge, fetal gonad and mesothelium. These data suggest that (1) this candidate is indeed a Wilms' tumour gene, (2) the associated genital abnormalities are pleiotropic effects of mutation in the Wilms' tumour gene itself, in support of recent genetic analysis, and (3) this gene has a specific role in kidney development and a wider role in mesenchymal-epithelial transitions.

Blotting, Northern↗
PubMed1990

Ultrasound of the normal nongravid uterus: correlation with gross and histopathology.

Accurate assessment of uterine size and significance of uterine enlargement are common clinical problems. We examined 156 patients by sonography prior to scheduled hysterectomy. Uterine volumes from normal-sized uteri were calculated from the sonograms using the equation of a prolate ellipsoid formula, and these calculated volumes were highly correlated with actual measured uterine volumes. Mean values and normal ranges of uterine weight were determined. These values are of particular value in postmenopausal patients in whom subjective evaluation of uterine enlargement is often difficult. When a sonographically enlarged, but otherwise normal uterus is discovered, it may contain a leiomyoma or other pathology not morphologically detectable by ultrasound.

Age Factors↗