Biomedical subjects

J Y Hu

Publications and source records attributed to J Y Hu.

44 records · Page 3Linked to original sources

PubMed1996

Protein-tyrosine kinase activation is required for lipopolysaccharide induction of interleukin 1beta and NFkappaB activation, but not NFkappaB nuclear translocation.

In human monocytes, interleukin 1beta protein production and steady state mRNA levels are increased in response to lipopolysaccharide, predominantly as a result of increased transcription of the interleukin 1beta gene. Expression of interleukin 1beta and other cytokines, such as interleukin 6 and tumor necrosis factor alpha, has been shown to be dependent on the activation of the transcription factor, NFkappaB. Since recent studies have shown that lipopolysaccharide-induced tyrosine kinase activation is not required for NFkappaB nuclear translocation, we sought to determine whether NFkappaB translocated in the absence of tyrosine kinase activity was active in stimulating transcription. We have found that, in the human pro-monocytic cell line, THP-1, the lipopolysaccharide-induced expression of interleukin 1beta is dependent on tyrosine kinase activation. Tyrosine kinases are not required for lipopolysaccharide-mediated nuclear translocation of NFkappaB. However, in the absence of tyrosine kinase activity, the ability of NFkappaB to stimulate transcription is impaired. This inhibition of transcription is specific for NFkappaB; in the absence of tyrosine kinase activity, AP-1-dependent transcription is enhanced. These results suggest that, while lipopolysaccharide-induced expression of inflammatory mediators requires tyrosine kinase activity, tyrosine kinase activity is not obligatory for lipopolysaccharide signal transduction.

Base Sequence↗

PubMed1996

Nonhomologous RNA-RNA recombination events at the 3' nontranslated region of the Sindbis virus genome: hot spots and utilization of nonviral sequences.

The mechanism of RNA-RNA recombination at the 3' nontranslated region (3'NTR) of the Sindbis virus (SIN) genome was studied by using nonreplicative RNA precursors. The 11.7-kb SIN genome was transcribed in vitro as two nonoverlapping RNA fragments. RNA-1 contained the entire 11.4-kb protein coding sequence of SIN and also carried an additional 1.8-kb nonviral sequence at its 3' end. RNA-2 carried the remaining 0.26 or 0.3 kb of the SIN genome containing the 3'NTR. Transfection of these two fragments into BHK cells resulted in vivo RNA-RNA recombination and release of infectious SIN recombinants. Eighteen plaque-purified recombinant viruses were sequenced to precisely map the RNA-RNA crossover sites at the 3'NTR. Sixteen of the 18 recombinants were found to be genetically heterogeneous at the 3'NTR. Two major clustered sites within the 3'NTR of RNA-2 were found to be fused to multiple locations on the nonviral sequence of RNA-1, resulting in insertions of 10 to 1,085 nucleotides at the 3'NTR. Sequence analysis of crossover sites suggested only limited homology and heteroduplex-forming capability between substrate RNAs. Analysis of additional 23 recombinant viruses generated by mutagenized donor and acceptor templates supports the occurrence of recombination hot spots on donor templates. Introduction of a 17-nucleotide rudimentary replicase recognition signal in the acceptor template alone did not induce the polymerase to reinitiate at the 17-nucleotide signal. Interestingly, deletion of a 24-nucleotide hot spot locus on the donor template abolished crossover events at one of the two sites and allowed the polymerase to reinitiate at the 17-nucleotide replicase recognition signal inserted at the acceptor template. The possible roles of RNA-protein and RNA-RNA interactions in the differential regulation of apparent pausing, template selection, and reinitiation are discussed.

Base Sequence↗

PubMed1994

A disease-related epitope of Torpedo acetylcholine receptor. Residues involved in I-Ab binding, self-nonself discrimination, and TCR antagonism.

Residues 146-162 of the Torpedo californica acetylcholine receptor alpha-subunit contain the immunodominant T cell epitope for experimental autoimmune myasthenia gravis-susceptible C57BL/6 mice. To develop potential therapeutic peptides, a detailed analysis of the epitope was undertaken. Truncated and substituted synthetic peptides were tested as stimulators of T cell clones and immune lymph node cells. Critical residues spanned positions 151-159. Y151 and V156 were critical for MHC binding. The results indicated a general motif for binding to I-Ab to be an aromatic or hydrophobic residue (preferentially Y or F) at position i followed by an uncharged residue at position (i + 5). Lysine was not tolerated at position (i + 8). Residues D152, K155, S157, and I158 were important T cell contact residues. A peptide corresponding to the murine 146-162 sequence, which differs from the Torpedo sequence at 5 residues, bound to I-Ab but was nonimmunogenic, consistent with the assigned TCR and I-Ab contact residues. These results suggest that tolerance is responsible for the lack of T cell cross-reactivity with the murine acetylcholine receptor. Substituted peptides were tested for the inhibition of T cell clone responses and for TCR antagonism. Although peptides substituted at residues 157 and 158 inhibited most clones, no single peptide could completely inhibit all clones or primed lymph node cells. These findings indicate that antagonist peptides may be useful in inhibiting T cell responses to complex Ag displaying a single immunodominant epitope. Multiple antagonists used in combination may be required for maximum inhibition of the response.

Amino Acid Sequence↗

PubMed1992

The fit of fixed partial dentures joined by infrared soldering.

This study determined the accuracy of fit of three-unit fixed partial dentures joined by an infrared soldering technique compared with one-piece fixed partial denture castings and individually cast crowns. Wax patterns of prepared Ivorine teeth, maxillary left central incisor and maxillary left canine, were injection molded; a plastic rod was used as a pontic. One group of patterns was cast as one-piece dentures; the other group was sectioned in the connector area, cast individually and then joined by infrared soldering. Castings were seated on their respective dies, embedded in epoxy resin, and sectioned. Gap distances between the casting and the die were measured at specified marginal sites with a profile projector. Results showed that the fit of infrared-soldered fixed partial dentures was significantly better than that of one-piece castings and was comparable with the fit of single crowns. The gap openings measured in all castings were within the range of clinical acceptability.

Crowns↗

PubMed1985