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R Luben

Publications and source records attributed to R Luben.

43 records · Page 3Linked to original sources
PubMed1998

Stimulation of Src family protein-tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cgamma2 activation in lymphoma B cells exposed to low energy electromagnetic fields.

Here, we present evidence that exposure of DT40 lymphoma B cells to low energy electromagnetic field (EMF) results in a tyrosine kinase-dependent activation of phospholipase Cgamma2 (PLC-gamma2) leading to increased inositol phospholipid turnover. B cells rendered PLC-gamma2-deficient by targeted disruption of the PLC-gamma2 gene as well as PLC-gamma2-deficient cells reconstituted with Src homology domain 2 (SH2) domain mutant PLC-gamma2 did not show any increase in inositol-1,4,5-trisphosphate levels after EMF exposure, providing direct evidence that PLC-gamma2 is responsible for EMF-induced stimulation of inositol phospholipid turnover, and its SH2 domains are essential for this function. B cells rendered SYK-deficient by targeted disruption of the syk gene did not show PLC-gamma2 activation in response to EMF exposure. The C-terminal SH2 domain of SYK kinase is essential for its ability to activate PLC-gamma2. SYK-deficient cells reconstituted with a C-terminal SH2 domain mutant syk gene failed to elicit increased inositol phospholipid turnover after EMF exposure, whereas SYK-deficient cells reconstituted with an N-terminal SH2 domain mutant syk gene showed a normal EMF response. LYN kinase is essential for the initiation of this biochemical signaling cascade. Lymphoma B cells rendered LYN-deficient through targeted disruption of the lyn gene did not elicit enhanced inositol phospholipid turnover after EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) mouse fyn gene into LYN-deficient B cells restored their EMF responsiveness. B cells reconstituted with a SH2 domain mutant fyn gene showed a normal EMF response, whereas no increase in inositol phospholipid turnover in response to EMF was noticed in LYN-deficient cells reconstituted with a SH3 domain mutant fyn gene. Taken together, these results indicate that EMF-induced PLC-gamma2 activation is mediated by LYN-regulated stimulation of SYK, which acts downstream of LYN kinase and upstream of PLC-gamma2.

Animals↗
PubMed1998

Mammographic parenchymal patterns and mode of detection: implications for the breast screening programme.

OBJECTIVES: To assess the effects of mammographic parenchymal patterns on the risk of breast cancer detected at first screen, second screen, and in the interval between these two screens. SETTINGS: A nested case-control study within a screening cohort in East Anglia was designed. The study group comprised 502 patients with cancer at the prevalence screening round, 198 patients with interval cancer, and 175 with cancer at the first incidence screen. These patients were matched with 2601 controls. METHODS: The mammographic parenchymal patterns of breast tissue were assessed according to Wolfe's classification. Statistical analysis was by conditional logistic regression. RESULTS: Overall, 67% of patients and 59% of controls were considered to have high risk pattern (P2 + DY) mammogram. The risk associated with P2 or DY mammographic patterns compared with N1 was higher for interval cancers (odds ratios (ORs) 2.2 and 2.4 respectively) than for screen detected cancers (ORs 1.7 and 1.1 respectively). For interval cancers in the first 18 months after the last negative mammogram, the risk was particularly high (ORs 3.8 for P2 and 4.1 for DY compared with N1). The high risk associated with P2 and DY patterns was concentrated on invasive ductal grade III cancers (ORs 2.7 and 3.8) rather than grade I or II cancers (ORs 1.6 and 1.2). CONCLUSIONS: The study strongly suggests that screening effectiveness is reduced for high risk parenchymal patterns which are associated with high grade cancers. Changes should aim at improving screening sensitivity for dense parenchymal patterns, and the diagnosis of high grade tumours.

Aged↗
PubMed1995

Exposure of B-lineage lymphoid cells to low energy electromagnetic fields stimulates Lyn kinase.

Here, we present evidence that exposure of B-lineage lymphoid cells to low energy electromagnetic fields (EMF) stimulates the protein tyrosine kinases Lyn and Syk, results in tyrosine phosphorylation of multiple electrophoretically distinct substrates, and leads to downstream activation of protein kinase C (PKC). EMF exposure enhances protein tyrosine phosphorylation in Syk deficient but not in Lyn-deficient B-lineage lymphoid cells and stimulates Lyn kinase activity in wild-type as well as Syk-deficient B-lineage lymphoid cells. These results indicate that activation of Lyn kinase is sufficient and mandatory for EMF-induced tyrosine phosphorylation in B-lineage lymphoid cells. The PKC activity increases later than the Lyn activity and pretreatment with the PTK inhibitors genistein or herbimycin A abrogates the EMF-induced PKC signal. Thus, stimulation of Lyn is a proximal and mandatory step in EMF-induced activation of PKC in B-lineage lymphoid cells. Our observations prompt the hypothesis that a delicate growth regulatory balance might be altered in B-lineage lymphoid cells by EMF-induced activation of Lyn.

Amino Acid Sequence↗
PubMed1983

A noninvasive functional lesion of the hypothalamo-pituitary axis for the study of growth hormone-releasing factor.

Rats were passively immunized with an antiserum against somatostatin and a monoclonal antibody against rat hypothalamic growth hormone-releasing factor (rGRF-mAb) which does not recognize the biologically active 1-40 amino acid fragment of hpGRF-44 (hpGRF-40). Using this paradigm we have observed that the pituitary possesses a resilient capacity to release growth hormone (GH) following repeated injections of hpGRF-40 and that this response follows a dose-dependent relationship.

Animals↗