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Biomedical subjects

F King

Publications and source records attributed to F King.

12 recordsLinked to original sources

Phosphatidylinositol 3-kinase inhibitor wortmannin blocks mitogenic activation of the transferrin receptor gene promoter in late G1.

Expression of the transferrin receptor is necessary for cells to progress through S-phase. The transferrin receptor gene promoter is activated as a delayed event following growth factor stimulation of quiescent fibroblasts. Serum stimulation in the presence of vanadate leads to superactivation of the transferrin receptor promoter, suggesting a role for tyrosine phosphorylation. Wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, a tyrosine kinase-regulated enzyme, blocks mitogen-dependent activation of the transferrin receptor promoter. Furthermore, wortmannin was able to block activation of this promoter when added several hours after serum stimulation of quiescent cells. This suggests that phosphatidylinositol 3-kinase may be required in mid to late G1 and that it is directly involved in a pathway leading to activation of the transferrin receptor promoter. This is further supported by the finding that the transferrin receptor promoter is much less responsive to mitogenic stimulation in cells that have been stably transfected with a dominant negative form of the phosphatidylinositol 3-kinase regulatory subunit. Activation of S6 kinase, an event known to be downstream of phosphatidylinositol 3-kinase activation, appears not to be involved in activation of the transferrin receptor promoter since no effect was observed by treatment of cells with rapamycin.

3T3 Cells

The role of infant factors in postnatal depression and mother-infant interactions.

A large group of infants of primiparous women who were at high risk fo r postnatal depression (N=188) and a smaller group of those at low risk (N=43) were assessed in the neonatal period using the Neonatal Behavioural Assessment Scale. Poor motor scores and high irritability were strongly predictive of the onset of maternal depression by eight weeks postpartum. These effects obtained after taking account of both maternal mood in the neonatal period and maternal perceptions of infant temperament. Poor motor scores and high levels of infant irritability in the neonatal period also predicted less optimal infant behaviour in face-to-face interactions with the mother at two months postpartum. Neonatal behaviour did not predict the persistence of depression, nor did it predict the quality of maternal behaviour in interaction with the infant.

Adult

Management guidelines for improvement of otolaryngology referrals from primary care physicians.

OBJECTIVE AND DESIGN: A prospective evaluation of the effectiveness of otolaryngology evaluation, treatment, and referral guidelines developed collaboratively by otolaryngologists and primary care physicians on referrals and access to otolaryngology. Comparisons of appropriate to unnecessary referrals, the percentage of patients referred with disorders addressed to those without disorders addressed in the guidelines, access to otolaryngology, and questionnaire evaluations of primary care physician and patient satisfaction were measured before and after guideline implementation. RESULTS: A significant decrease in appropriate to unnecessary referrals was seen, from 55% before to 12% after guidelines. The percentage of patients seen within 1 month of scheduling improved from 39% to 59%. Guideline-addressed disorders decreased from 63% to 40%. The need for patients to see another physician for the referred symptom while waiting to see an otolaryngologist decreased from 31% to 3%. Patient satisfaction with wait times improved. Eighty-six percent of the primary care physicians used the guidelines, and 85% wanted to expand the guidelines to other specialty areas. CONCLUSIONS: Management and referral guidelines are effective in improving patient access and the ratio of appropriate to unnecessary referrals. Such guidelines are well accepted and used by primary care practitioners in this setting.

Appointments and Schedules

SH2 domains recognize specific phosphopeptide sequences.

A phosphopeptide library was used to determine the sequence specificity of the peptide-binding sites of SH2 domains. One group of SH2 domains (Src, Fyn, Lck, Fgr, Abl, Crk, and Nck) preferred sequences with the general motif pTyr-hydrophilic-hydrophilic-Ile/Pro while another group (SH2 domains of p85, phospholipase C-gamma, and SHPTP2) selected the general motif pTyr-hydrophobic-X-hydrophobic. Individual members of these groups selected unique sequences, except the Src subfamily (Src, Fyn, Lck, and Fgr), which all selected the sequence pTyr-Glu-Glu-Ile. The variability in SH2 domain sequences at likely sites of contact provides a structural basis for the phosphopeptide selectivity of these families. Possible in vivo binding sites of the SH2 domains are discussed.

Amino Acid Sequence

Postdischarge formula consumption in infants born preterm.

In 31 infants born preterm and formula fed ad libitum, all milk intake was weighed from hospital discharge to nine months post-term. Mean daily milk intake was high, reaching 230 g/kg before four weeks post-term and was still over 150 g/kg beyond six months. Five of the 31 infants (16%) consumed 300-350 g/kg; 50% 'voluntarily' consumed more than upper recommended limits for energy intake and 35% did so for protein intake.

Body Weight

Identification, isolation, and characterization of a novel cytotoxin in murine cytolytic lymphocytes.

Murine cytotoxic T lymphocytes contain, in addition to the cytotoxic pore-forming protein perforin, another cytolytic factor localized in both cytoplasm and granules. Like perforin, this CTL cytotoxin lyses a variety of tumor cells; unlike perforin, it is stable in the presence of calcium, requires several hours to induce maximal lytic activity, and is antigenically related to the previously described tumor necrosis factor (TNF) and lymphotoxin (LT). However, it differs from TNF and LT in a number of biochemical and functional properties. TNF- and LT-specific cDNA probes did not hybridize with any CTL-specific message, indicating that the CTL cytotoxin is distinct from those two factors. It has an apparent Mr of 50 and 70 kd under reducing and nonreducing conditions, respectively, is secreted by secretagogue-stimulated CTLs, and causes DNA fragmentation in several targets, a phenomenon previously attributed to target cell damage by CTLs. These results suggest that killing by lymphocytes may encompass multiple mechanisms and polypeptides.

Animals