PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Restrictive”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources
PubMed2004

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors.

We have recently shown that interleukin-2 (IL-2)-activated CD8(+)CD44(hi) cells from normal mice express both adaptive and innate immune system receptors and specifically kill syngeneic tumor cells, particularly those that express NKG2D ligands. Here we show that CD8+ T cells from antigen-expressing H-Y T-cell receptor (TCR) transgenic mice also exhibit characteristics of both T cells and natural killer (NK) cells. Interaction with cognate self-antigen was required for the optimal expansion of these cells in peripheral lymphoid tissues. Although these cells possess a higher activation threshold relative to naive T cells, they can be activated by cytokine alone in vitro. They also undergo bystander proliferation in response to a bacterial infection in vivo. Interestingly, upon activation, the cells express the NKG2D receptor as well as the DNAX activation protein 12 (DAP12) adaptor protein. We provide evidence that NKG2D can act additively with the TCR in the killing of target cells, and it can also function as a directly activating receptor in non-major histocompatibility complex (MHC)-restricted killing of target cells. These properties of CD8+ T cells from H-Y TCR transgenic mice are remarkably similar to CD8(+)CD44(hi) cells that are found in normal mice. The H-Y TCR transgenic mice provide a well-defined system for characterizing the developmental biology and function of these cells.

Animals↗
PubMed1999

Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: molecular evidence for "placental hyperoxia" in intrauterine growth restriction.

Early placental development occurs in an environment of relative hypoxia. Hypoxia promotes angiogenesis and up-regulates vascular endothelial growth factor (VEGF) expression while it down-regulates placenta growth factor (PIGF) that possess 53% homology with VEGF. Morphological studies show poor placental vascular development and an increase in the mitotic index of cytotrophoblasts in intrauterine growth restriction (IUGR). We hypothesized that the reported relatively high oxygen level in the intervillous space in contact with IUGR placental villi will limit angiogenesis by changes in VEGF and PIGF expression and function. Western immunoblot analysis demonstrates a diametric expression of PIGF and VEGF proteins throughout pregnancy with PIGF levels increasing and VEGF levels decreasing, consistent with placental oxygenation. In IUGR placentae, the ratio of PIGF/GAPDH mRNA was increased by 2.3-fold (p < 0.03) and PIGF protein levels were also increased, (p < 0.05) as compared with gestationally-matched normal placentae. PIGF mRNA and protein were localized to the trophoblast bilayer and villous mesenchyme of the human placenta throughout gestation. In vitro studies demonstrated that increasing oxygen tension (hyperoxia) up-regulated PIGF protein in term placental villous explants, whereas hypoxic culture of a term trophoblast choriocarcinoma cell line (BeWo) down-regulated PIGF mRNA and protein and VEGFR-1 (Flt-1) autophosphorylation. The addition of PIGF-1 to a spontaneously transformed first trimester cytotrophoblast cell line stimulated DNA synthesis while PIGF-2 had little effect. VEGF and PIGF exert their biological actions by means of a common receptor VEGFR-1. In the first trimester trophoblast cells, PIGF-1 increased the association of phosphorylated extracellular signal-related kinase (ERK) with VEGFR-1 immunoprecipitates while both PIGF-1 and PIGF-2 also potentiated endogenous VEGF mediated association of phosphorylated extracellular related kinase (ERK) with VEGFR-2 (KDR). More importantly, the addition of PIGF-1 had little effect while PIGF-2 inhibited cell growth in cultured endothelial cells derived from human umbilical vein. Nitric oxide (NO) is reported to promote angiogenesis and PIGF-2 inhibited the basal release of NO from the first trimester trophoblast. The tissue expression and functional studies support the hypothesis of "placental hyperoxia" in early-onset IUGR because hypoxia down-regulates trophoblast PIGF levels, PIGF expression is increased in IUGR, and PIGF-2 inhibits endothelial cell growth. Taken together, these changes provide a cellular explanation for the observed poor angiogenesis in the pathogenesis of IUGR and show that the two PIGF isoforms may modulate trophoblast and endothelial cell function differently, possibly through potentiation of VEGF mediated activation of VEGF-2.

Cell Line↗
PubMed1993

Structural complexity of antigenic determinants for class I MHC-restricted, hapten-specific T cells. Two qualitatively differing types of H-2Kb-restricted TNP epitopes.

The understanding of chemically induced allergic or autoimmune disorders requires a detailed structural analysis of the antigenic determinants produced by chemical modification of cells. Using H-2Kb-restricted, TNP-specific cytotoxic mouse T cells and synthetic, Kb-associating TNP-peptides, we define at least two types of functionally distinguishable TNP epitopes. The first one contains TNP in position 4 of different Kb-binding octapeptides and is detected by the majority of in vitro-induced TNP/Kb-specific CTL. This immunodominant structure could be imitated by oligo-glycine based "designer peptides," containing only the Kb "anchor-residues" and TNP-Lys in position 4. A second, qualitatively different determinant is created by TNP-Lys in position 7. T cells of such specificity are rare and recognize TNP only in context of unique peptide sequences. In this case, designer peptides revealed a complex antigenic determinant comprised of TNP-7 and unmodified amino acids in positions 3 and 4. Chances to form a particular determinant of this type by chemical modification are small and, thus, each clone will detect only few epitopes per cell. In contrast, the dominant TNP-4 epitope on differing peptides results in highly repetitive determinants. TCR specific for the rare TNP-7 structure were found to simultaneously contact TNP in position 7 and unmodified amino acids in positions 3 and 4. However, they may also react individually with either the peptide or the hapten part of these complex determinants. This implies a potentially important role of such structures in the induction of autoimmunities: resting T cells, bearing low affinity receptors to self peptides may be activated by peptide/hapten complexes and allow recall responses to the isolated peptide epitope of the unmodified self peptide.

Amino Acid Sequence↗
PubMed2004

Clinical trial experience with fat-restricted vs. carbohydrate-restricted weight-loss diets.

It is unlikely that one diet is optimal for all overweight or obese persons. Both low-fat and low-carbohydrate diets have been shown to induce weight loss and reduce obesity-related comorbidities. Low-carbohydrate diets cause greater short-term (up to 6 months) weight loss than low-fat diets, but the long-term clinical safety and efficacy of these diets has not been studied.

Body Composition↗
PubMed1989

The fokI restriction-modification system. I. Organization and nucleotide sequences of the restriction and modification genes.

A DNA fragment that carried the genes coding for FokI endonuclease and methylase was cloned from the chromosomal DNA of Flavobacterium okeanokoites, and the coding regions were assigned to the nucleotide sequence by deletion analysis. The methylase gene was 1,941 base pairs (bp) long, corresponding to a protein of 647 amino acid residues (Mr = 75,622), and the endonuclease gene was 1,749 bp long, corresponding to a protein of 583 amino acid residues (Mr = 66,216). The assignment of the methylase gene was further confirmed by analysis of the N-terminal amino acid sequence. The endonuclease gene was downstream from the methylase gene in the same orientation, separated by 69 bp. The promoter site, which could be recognized by Escherichia coli RNA polymerase, was upstream from the methylase gene, and the sequences adhering to the ribosome-binding sequence were identified in front of the respective genes. Analysis of the gene products expressed in E. coli cells by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the molecular weights of both enzymes coincided well with the values estimated from the nucleotide sequences, and that the monomeric forms were catalytically active. No significant similarity was found between the sequences of the two enzymes. Sequence comparison with other related enzymes indicated that FokI methylase contained two copies of a segment of tetra-amino acids which is characteristic of adenine-specific methylase.

Amino Acid Sequence↗