Biomedical subjects

J Yen

Publications and source records attributed to J Yen.

6 recordsLinked to original sources

PubMed1992

Transformation by FosB requires a trans-activation domain missing in FosB2 that can be substituted by heterologous activation domains.

Two functionally distinct proteins derived from the FosB gene by alternative splicing have recently been described. FosB protein transforms fibroblasts efficiently, whereas FosB2 protein, a carboxy-terminally truncated form of FosB, does not, despite the fact that both proteins can participate in high-affinity, sequence-specific DNA binding as part of a heterodimeric complex with c-Jun protein. We show here that the functional difference between these proteins is the result of the presence of a potent proline-rich transcriptional activation domain in the carboxy-terminal amino acids unique to FosB. This conclusion is supported by three lines of evidence: (1) Mutations in the carboxy-terminal region of FosB that impair transcriptional activation also reduce transforming potential, despite the fact that DNA binding as part of a complex with c-Jun is not affected; (2) the carboxy-terminal region unique to FosB functions as an activation domain when fused to the DNA-binding domain of GAL4; and (3) transforming potential can be conferred on FosB2 by fusing any of several different well-characterized trans-activation domains. These results identify an additional functional requirement for transformation by Fos proteins and have implications for the mechanism(s) of mitogenic signaling by the AP-1 transcription complex.

Amino Acid Sequence↗

PubMed1992

[Vascular relationships of the trigeminal root with trigeminal neuralgia].

The vascular relationships of 79 trigeminal nerves exposed surgically for treatment of trigeminal neuralgia were studied. 87 etiologic vessels (vein in 28, artery in 59) were found and the most common arterial and venous etiologic vessel was the superior cerebellar artery (33/59) and petrous vein (16/28) respectively. The result provided some clinic data for microvascular decompression in treatment of idiopathic trigeminal neuralgia.

Adult↗

PubMed1991

An alternative spliced form of FosB is a negative regulator of transcriptional activation and transformation by Fos proteins.

Two forms of FosB transcript and their products can be identified in mouse NIH 3T3 cells following serum induction. The larger RNA codes for a 338-amino acid protein, whereas the smaller RNA results from the removal of an additional 140 nucleotides from FosB mRNA by alternative splicing. This alternative splicing event places a stop codon following the "leucine zipper" region and results in a shorter protein (FosB2) of 237 amino acids that lacks 101 amino acids at the carboxyl terminus. FosB2 is able to form heterodimers with c-Jun and bind to an AP-1 site but is not able to activate the transcription of promoters containing AP-1 sites. Furthermore, FosB2 can not only suppress the transcriptional activation by c-Fos and c-Jun of promoters containing an AP-1 site but also interferes with the transforming potential of viral and cellular Fos proteins. We propose that FosB2 protein functions as a trans-negative regulator.

Amino Acid Sequence↗

PubMed1991

A rapid in vitro cytotoxicity assay for the detection of tumor necrosis factor on human BT-20 cells.

This report describes a rapid, reproducible in vitro bioassay to quantitate the cytotoxic activity of human tumor necrosis factor-alpha using a human rather than murine cell line in the absence of metabolic inhibitors. The target cells are BT-20 (breast carcinoma) cultured at 39 degrees C in the presence of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) in 96-well microtiter plates for 2 days. Cytotoxicity is measured by the crystal violet dye uptake of the remaining viable cells. This bioassay is sensitive to 1.5 ng/ml of rHuTNF-alpha, with an assay range to 130 ng/ml. Samples spiked into human plasma are measurable from 0.5 to 150 ng/ml. The specificity of this cytotoxic effect on the BT-20 cell line was demonstrated using rHuTNF-alpha neutralizing antibodies. A panel of cytokines including interferons, interleukins, and tumor necrosis factors was also analyzed using this assay system. Of the cytokines assayed, only recombinant murine tumor necrosis factor-alpha and recombinant human tumor necrosis factor-beta demonstrated measurable cytotoxic activity when assayed independently, while recombinant human interferon-gamma was the only cytokine to demonstrate greater than additive activity in combination with rHuTNF-alpha. The simplicity and reproducibility of this assay on a human cell line makes it useful for the routine determination of the biological activity of human tumor necrosis factor-alpha.

Antigen-Antibody Reactions↗

PubMed1978

Direct administration of methotrexate into the central nervous system of primates. Part 2: Distribution of 3H methotrexate after intrathecal lumbar injection.

The kinetics of distribution of 3H methotrexate (3HMTX) in the central nervous system, plasma, and urine after intraventricular, lumbar percutaneous puncture, and spinal catheter injections were compared. Levels of 3HMTX in whole brain after lumbar percutaneous injection were 40 times less than after intraventricular injection. Injection of 3HMTX via a spinal catheter increased the level of 3HMTX in whole brain but this was still tenfold less than after direct intraventricular instillation. Also, it was found that a disproportionately high amount of 3HMTX was in the brain-stem-cerebellum region which would further reduce the concentration of methotrexate in the cerebral hemispheres. Both intraventricular and lumbar spinal catheter administration of 3HMTX produced 3HMTX levels greater than 10(-6)M (moles/kg wet weight) in spinal cord tissue as measured by 3H specific activity between 2 to 8 hours after injection. Administration by lumbar percutaneous puncture, however, rarely resulted in this suggested therapeutic level of 10(-6)M. Initial 3HMTX levels in plasma after lumbar percutaneous instillation was 24 times greater than after intraventricular or lumbar spinal catheter injections. This indicated significant and unavoidable extradural leakage after lumbar percutaneous puncture, which may account for the substantially lower levels of 3HMTX in the brain and spinal cord tissue. It is concluded that intraventricular instillation of methotrexate is the best route of administering the drug to achieve therapeutic levels of methotrexate in both whole brain and throughout the spinal cord.

Animals↗

PubMed1975

Competition radioimmunoassay for mason-pfizer monkey virus: comparison with recent isolates.

The major core protein of Mason-Pfizer monkey virus was purified by DEAE ion exchange column chromatography and shown to be 27,000 daltons (p27). Following the characterization of monospecific antisera prepared against p27, a radioimmunoassay was developed with these reagents and competition experiments were done with come of the recent M-PMY-like isolates as well as with other oncornaviruses. Results suggest that three of the viruses tested, AO, X-381 and FTP-1, are similar to M-PMV while J-96 virus is related, but not identical, to M-PMV. It is also shown that competition RIA can be used successfully to detect the presence of viral proteins in tissue homogenates and cell extracts.

Animals↗