Occult bony metastatic disease demonstrated on labeled leukocyte scintigraphy.
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Aged↗
Biomedical subjects
Lily Shen
Publications and source records attributed to Lily Shen.
Subcutaneous panniculitis-like T cell lymphoma demonstrated on gallium-67 scintigraphy.
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Citrates↗
Thyroid dysfunction during interferon alpha therapy for chronic hepatitis C.
Interferon-alpha therapy is well known to induce a wide range of thyroid dysfunction. A 22-year-old woman with chronic hepatitis C developed overt hyperthyroidism while on interferon-alpha and ribavirin therapy. Tc-99m thyroid scintigraphy demonstrated virtually absent tracer uptake consistent with subacute thyroiditis. Ten months after starting antiviral therapy, overt hyperthyroidism recurred. Repeat thyroid scintigraphy revealed diffusely increased tracer uptake throughout the thyroid gland consistent with Graves disease. This is an unusual case of 2 forms of hyperthyroidism-confirmed scintigraphically and occurring in the same patient over time while on interferon-alpha therapy.
Adult↗
Stress granule assembly is mediated by prion-like aggregation of TIA-1.
TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells. The PRD of TIA-1 exhibits many characteristics of prions: concentration-dependent aggregation that is inhibited by the molecular chaperone heat shock protein (HSP)70; resistance to protease digestion; sequestration of HSP27, HSP40, and HSP70; and induction of HSP70, a feedback regulator of PRD disaggregation. Substitution of the PRD with the aggregation domain of a yeast prion, SUP35-NM, reconstitutes SG assembly, confirming that a prion domain can mediate the assembly of SGs. Mouse embryomic fibroblasts (MEFs) lacking TIA-1 exhibit impaired ability to form SGs, although they exhibit normal phosphorylation of eukaryotic initiation factor (eIF)2alpha in response to arsenite. Our results reveal that prion-like aggregation of TIA-1 regulates SG formation downstream of eIF2alpha phosphorylation in response to stress.
Amino Acid Sequence↗
Arthritis suppressor genes TIA-1 and TTP dampen the expression of tumor necrosis factor alpha, cyclooxygenase 2, and inflammatory arthritis.
TIA-1 and TTP are AU-rich element-binding proteins that prevent the pathological overexpression of tumor necrosis factor alpha (TNF-alpha). TIA-1 inhibits the translation of TNF-alpha transcripts, whereas TTP promotes the degradation of TNF-alpha transcripts. Here we show that TIA-1 and TTP function as arthritis suppressor genes: TIA-1(-/-) mice develop mild arthritis, TTP(-/-) mice develop severe arthritis, and TIA-1(-/-)TTP(-/-) mice develop very severe arthritis. Peritoneal macrophages derived from all three genotypes overexpress cyclooxygenase 2 and TNF-alpha. Surprisingly, lipopolysaccharide-activated TIA-1(-/-)TTP(-/-) macrophages secrete less TNF-alpha protein than either TIA-1(-/-) or TTP(-/-) macrophages. In these mice, arthritogenic cytokine may be produced by neutrophils that accumulate in the bone marrow and peripheral blood. Our results suggest that TIA-1 and TTP are genetic modifiers of inflammatory arthritis that can alter the spectrum of cells that produce arthritogenic cytokines.
Animals↗