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1.  Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells. 
Molecular and Cellular Biology  1994;14(3):1845-1851.
We have previously shown that the signal peptideless cytokine interleukin 1 alpha (IL-1 alpha) may play a role as an intracellular regulator of human endothelial cell senescence (J. A. M. Maier, P. Voulalas, D. Roeder, and T. Maciag, Science 249:1570-1574, 1990). To investigate the potential intracellular function of IL-1 alpha, transformed endothelial cells were transfected with the human cDNAs that code for the two forms of IL-1 alpha, the precursor molecule IL-1(1-271) and the mature protein IL-1(113-271). The subcellular localization of the two different polypeptides was investigated directly or by using chimeric genes constructed by fusion of different fragments of the IL-1 alpha gene and the beta-galactosidase open reading frames. The IL-1(113-271) protein was cytoplasmic, while IL-1(1-271) was nuclear. The basic cluster at the NH2 terminus of IL-1, KVLKKRR, has been shown to mediate IL-1 alpha nuclear targeting. Moreover, nuclear localization of IL-1 alpha correlates with impaired cell growth and expression of some IL-1 alpha-inducible genes. These results suggest that transport of endogenous IL-1(1-271) into the nucleus is required for it to modulate endothelial cell function.
PMCID: PMC358542  PMID: 8114717
2.  In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. 
Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo. We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis. Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia. Significantly less or equivocal staining was noted in OA and normal human synovia. Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats. In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis. COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained. Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats. These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids.
PMCID: PMC442824  PMID: 1729286
3.  Technique-related variation in results of FANA tests. 
Annals of the Rheumatic Diseases  1984;43(5):755-757.
We compared the reliability and reproducibility of three tests for fluorescent antinuclear antibodies (FANA) that are routinely performed in our laboratory. Sera from 72 patients, selected according to diagnosis (SLE in 28, RA in 12, and other connective-tissue diseases in 33), and from 32 healthy controls were tested with all three assays. There were wide variations between the results obtained with these tests. The variations did not reflect sensitivity or degree of standardisation (reproducibility on retesting was greater than 95%) and appeared to be inherent in the techniques. Clinicians should be aware of the technique-related differences in FANA assays.
PMCID: PMC1001522  PMID: 6388514
4.  A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide and targets it to CD4+ cells. 
Nucleic Acids Research  1995;23(22):4603-4607.
An approach was sought to increase the half-life and target cell specificity of antisense oligodeoxynucleotides (oligos). A monoclonal antibody (MAb) was derived from mice immunised with an oligo complementary to a region (1-20) of the HIV genome. This MAb exerts a protective effect on the oligo from the degradation induced by plasma exonucleases in vitro and in vivo. Moreover the anti-oligo MAb dissociates from the oligo in the presence of its complementary sequence to allow hybridization of the two complementary strands. To direct the oligo to CD4+ cells the anti-oligo MAb was cross-linked to an anti-CD4 MAb. The heteroaggregate determines a 5-fold increase in the cellular membrane binding of the oligo to CD4+ lymphocytes. These findings suggest a new approach to enhancing the therapeutic action and the target specificity of antisense oligodeoxynucleotides useful for the selective inhibition of HIV replication in vivo.
PMCID: PMC307432  PMID: 8524649
Rhesus monkeys with experimental Plasmodium knowlesi infections of varying duration were treated with sodium sulfathiazole to sterilize the infection and after differing lengths of time were reinoculated intraperitoneally with homologous strains of the plasmodium, for the purpose of determining whether there is any acquired immunity to malaria in hosts from whom all parasites have been removed. Two monkeys, one receiving sulfathiazole on the 2nd day of acute infection and the other on the 4th day, had no immunity at the time of reinoculation, 3 weeks and 10 weeks later, respectively. Both developed infections which followed the course usual in an acute attack in a normal monkey. In monkeys which survived acute infection with the aid of immune serum or quinine and in which a naturally acquired immunity had developed to the point where the acute infection was converted into a chronic one, there was an undoubted persistence of partial immunity up to about a year after sterilization of the infection with sulfathiazole, as indicated by recovery of reinoculated animals after mild or moderately severe infections differing widely in characteristics from the infection in the normal monkey. The end point at which immunity disappears seems to be independent of the length of the chronic infection.
PMCID: PMC2135385  PMID: 19871378

Results 1-5 (5)