Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here on stable prepackaging cell lines which can be converted into packaging cell lines for high-titer vesicular stomatitis virus G protein (VSV-G)-pseudotyped retrovirus vectors by the introduction of Cre recombinase-expressing adenovirus. The generated prepackaging cell lines constitutively express the gag-pol genes and contain an inducible transcriptional unit for the VSV-G gene. From this unit, the introduced Cre recombinase excised both a neomycin resistance (Neo(r)) gene and a poly(A) signal flanked by a tandem pair of loxP sequences and induced transcription of the VSV-G gene from the same promoter as had been used for Neo(r) expression. By inserting an mRNA-destabilizing signal into the 3' untranslated region of the Neo(r) gene to reduce the amount of Neo(r) transcript, we were able efficiently to select the clones capable of inducing VSV-G at high levels. Without the introduction of Cre recombinase, these cell lines produce neither VSV-G nor any detectable infectious virus at all, even after the transduction of a murine leukemia virus-based retrovirus vector encoding beta-galactosidase. They reproducibly produced high-titer virus stocks of VSV-G-pseudotyped retrovirus (1.0 x 10(6) infectious units/ml) from 3 days after the introduction of Cre recombinase. We also present evidence that VSV-G-producing cells are still fully susceptible to transduction by VSV-G pseudotypes. However, in this vector-producing system, which regulates VSV-G pseudotype production in an all-or-none manner, the integration of vector DNA into packaging cell lines would be minimized. We further show that heparin significantly inhibits retransduction of VSV-G pseudotypes in the culture fluids of packaging cell lines, leading to a two- to fourfold increase in the yield of the pseudotypes after induction. This vector-producing system was very stable and should be advantageous in human gene therapy.
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PMID:A new system for stringent, high-titer vesicular stomatitis virus G protein-pseudotyped retrovirus vector induction by introduction of Cre recombinase into stable prepackaging cell lines. 944 7

A 6-month-old boy was diagnosed as having Crohn's disease (CD) by the endoscopic examination. Primary immunodeficiency syndrome was initially suspected due to a refractory infection that occurred just after birth and a family history that his older brother died at the age of 3 months of septicemia associated with perirectal abscess. Thalidomide was used because conventional medical treatment by steroids and immunosuppressives was ineffective. Thalidomide improved the symptoms of diarrhea, abdominal pain, high fever and fistula, and the PCDAI score decreased markedly from 45 to 15. Although thalidomide was discontinued after three months because of the onset of side effects, including edema, rash and the peripheral neuropathy, the effect on the fistula closure was maintained over a long period of time. Further studies will be necessary to determine the dosage of thalidomide that does not elicit side effects, but thalidomide seems to be effective in patients with refractory CD. Infantile CD is very rare and the diagnosis is often delayed. CD is generally resistant to medical treatment. More detailed information of infantile CD will be needed to elucidate the pathogenesis of this disease and progress of treatment. Recently the incidence of inflammatory bowel diseases has increased. CD should be suspected in any infant with the perianal lesion (fissures, fistula, skin tag and abscesses) especially when prolonged gastrointestinal symptoms, stomatitis or fever coexist.
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PMID:[Thalidomide therapy for infantile-onset Crohn's disease]. 1586 68