Biomedical subjects

D B Lewis

Publications and source records attributed to D B Lewis.

At least 55 records · Page 3Linked to original sources

PubMed1987

Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases.

The lymphocyte-specific protein tyrosine kinase pp56lck, encoded by a member of the src gene family, is implicated in the control of T-cell growth and differentiation. Purified resting human T lymphocytes contain appreciable levels of lck mRNA and of pp56lck. Upon activation of these T cells, levels of lck mRNA and of pp56lck promptly decline. These reductions in lck mRNA and protein expression are closely correlated with the induction of lymphokine production. Both require identical stimuli and follow a similar time course of response. Down-regulation of lck expression, however, is not correlated with proliferation. Our results provide an example of regulation of a src-like protein tyrosine kinase in a normal fully differentiated cell population and suggest that modulation of lck RNA and protein expression is an important feature of the lymphocyte activation sequence leading to lymphokine production.

Adult↗

PubMed1987

Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin.

Protein-tyrosine kinases are implicated in the control of cell growth by virtue of their frequent appearance as products of retroviral oncogenes and as components of growth factor receptors. Here we report the characterization of a novel human protein-tyrosine kinase gene (hck) that is primarily expressed in hematopoietic cells, particularly granulocytes. The hck gene encodes a 505-residue polypeptide that is closely related to pp56lck, a lymphocyte-specific protein-tyrosine kinase. The exon breakpoints of the hck gene, partially defined by using murine genomic clones, demonstrate that hck is a member of the src gene family and has been subjected to strong selection pressure during mammalian evolution. High-level expression of hck transcripts in granulocytes is especially provocative since these cells are terminally differentiated and typically survive in vivo for only a few hours. Thus the hck gene, like other members of the src gene family, appears to function primarily in cells with little growth potential.

Amino Acid Sequence↗

PubMed1986

Reduced interferon-gamma mRNA levels in human neonates. Evidence for an intrinsic T cell deficiency independent of other genes involved in T cell activation.

IFN-gamma mRNA levels in human neonatal blood mononuclear cells or highly purified T cells were markedly lower than those of adult cells after incubation with Con A and PMA. In contrast, IL-2, IL-2-R, and T3 delta chain mRNA levels were kinetically and quantitatively similar in neonatal and adult T cells. The peak amount of IFN-gamma and IL-2 mRNA correlated well with IFN-gamma and IL-2 detected in supernatants of both neonatal and adult T cells. These results suggest that reduced IFN-gamma mRNA levels in neonatal T cells is due to an intrinsic deficiency at the pretranslational level and indicate that the magnitude of IL-2 and IFN-gamma gene expression can be independently modulated pretranslationally.

Genes↗

PubMed1986

The preoperative liver scan and surgical decision-making in patients with colorectal cancer.

The influence of preoperative liver scans and liver function tests on surgical decision-making was analyzed in 196 patients who underwent surgical therapy for colorectal cancer. One hundred and thirteen patients who had preoperative liver scans were compared with 83 patients who did not. No statistically significant difference existed between the liver scan group and the nonscan group in terms of when surgical decision-making occurred. Likewise, the results of the liver scan did not influence when operative decisions were made. The majority of decision-making occurred intraoperatively when ultimate confirmation of the presence or absence of hepatic metastases was made. Presumptive surgical decisions were made preoperatively, but final decisions occurred intraoperatively when all relevant patient data could be correlated. Liver scanning has limited usefulness in the preoperative evaluation of patients with colon cancer as it does not affect decision-making and is much more costly than liver function testing.

Adult↗

PubMed1986

Nosocomial Klebsiella pneumoniae colonization in a neonatal special care unit.

A clinical study is reported of nosocomial Klebsiella pneumoniae colonization and infection in a neonatal special care unit in Barbados. Of the 14 infants who were affected nine were symptomatic and two died (15%) during a 9-day period. This outbreak appeared to have been an indirect result of an acute shortage of nursing personnel coupled with a breakdown in adequate handwashing techniques. We feel that periodic review and continuous reinforcement of infection control policies in areas with patients at high risk of nosocomial infection, such as the neonatal unit, are of paramount importance.

Barbados↗

PubMed1986

Decreased production of interferon-gamma by human neonatal cells. Intrinsic and regulatory deficiencies.

Human neonatal lymphocytes produced little macrophage activation factor in response to mitogens. This correlated with decreased production of interferon-gamma (IFN gamma): adult lymphokines contained 894.2 +/- 177.1 U/ml, whereas neonatal cord and peripheral lymphokines contained 66.9 +/- 17.0 and 116.7 +/- 29.6 U/ml by bioassay. Results by radioimmunoassay (RIA) for IFN gamma were similar. In contrast, the interleukin 2 content of cord lymphokines was greater (P less than 0.01) and that of neonatal peripheral blood lymphokines similar to that of adults. Interleukin 1 production and interleukin 2 receptor expression and affinity were similar for adult and neonatal cells. Interleukins 1 and 2 in amounts comparable to those in adult lymphokines did not increase production of macrophage activation factor or IFN gamma by neonatal cells. Neonatal cells did not contain intracellular IFN or degrade exogenous IFN. Excess suppressor activity was not found in neonatal cultures. Addition of IFN alpha, 10,000-50,000 U/ml of interleukin 2 or phorbol myristate acetate (PMA) to cord mononuclear cells or of adult monocytes or PMA to cord T cells increased IFN gamma production compared to cells stimulated with concanavalin A (ConA) alone. Nevertheless, under optimal conditions (T cells + PMA + Con A), adult cells produced much more IFN gamma (1,360 +/- 261 U/ml by RIA) than cord cells (122 +/- 37 U/ml). Staphylococcal enterotoxin A (SEA) stimulated cord cell IFN gamma production at low cell densities; nevertheless, adult cells produced more IFN in response to SEA 1,341 +/- 350 U/ml) than cord cells (350 +/- 33 U/ml). Decreased production of IFN gamma by neonatal cells appears to be due both to differences in their intrinsic capacity to produce IFN gamma and to differences in regulatory mechanisms.

Concanavalin A↗

PubMed1984