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R Fulton

Publications and source records attributed to R Fulton.

At least 55 records · Page 3Linked to original sources
PubMed1994

Genetic determinants of feline leukemia virus-induced lymphoid tumors: patterns of proviral insertion and gene rearrangement.

The genetic basis of feline leukemia virus (FeLV)-induced lymphoma was investigated in a series of 63 lymphoid tumors and tumor cell lines of presumptive T-cell origin. These were examined for virus-induced rearrangements of the c-myc, flvi-2 (bmi-1), fit-1, and pim-1 loci, for T-cell receptor (TCR) gene rearrangements, and for the presence of env recombinant FeLV (FeLV-B). The myc locus was most frequently affected in naturally occurring lymphomas (32%; n = 38) either by transduction (21%) or by proviral insertion (11%). Proviral insertions were also common at flvi-2 (24%). The two other loci were occupied in a smaller number of the naturally occurring tumors (fit-1, 8%; pim-1, 5%). Examination of the entire set of tumors showed that significant numbers were affected at two (19%) or three (5%) of the loci. Occupation of the fit-1 locus was observed most frequently in tumors induced by FeLV-myc strains, while flvi-2 insertions occurred with similar frequency in the presence or absence of obvious c-myc activation. These results suggest a hierarchy of mutational events in the genesis of feline T-cell lymphomas by FeLV and implicate insertion at fit-1 as a late progression step. The strongest links observed were with T-cell development, as monitored by rearrangement status of the TCR beta-chain gene, which was positively associated with activation of myc (P < 0.001), and with proviral insertion at flvi-2 (P = 0.02). This analysis also revealed a genetically distinct subset of thymic lymphomas with unrearranged TCR beta-chain genes in which the known target loci were involved very infrequently. The presence of env recombinant FeLV (FeLV-B) showed a negative correlation with proviral insertion at fit-1, possibly due to the rapid onset of these tumors. These results shed further light on the multistep process of FeLV leukemogenesis and the relationships between lymphoid cell maturation and susceptibility to FeLV transformation.

Animals↗
PubMed1994

Regional deposition of nebulized hypodense nonisotonic solutions in the human respiratory tract.

Deposition of nonisotonic therapeutic and diagnosis aerosols can cause changes in airway fluid composition and bronchoconstriction in sensitive subjects. "Hypodense" aerosols containing a relatively low concentration of droplets in the carrier air were used in the studies of regional deposition of radiolabelled nebulized solutions of hypo- and hypertonic saline, in order to investigate whether the number of droplets per volume of carrier can affect deposition. Solutions with and without 0.5% nedocromil sodium were nebulized in order to examine the effects of a potential modifier of the rates of heat and mass transfer. The deposition was quantified using penetration index (PI) calculated from images obtained by single photon emission computerized tomography (SPECT) in 11 healthy volunteers per study. There was an increase in the penetration index (10.9%, for the saline only; 15.5%, for the nedocromil study) of the hypotonic compared to the hypertonic aerosol, although the initial size distribution of both types of aerosols was very similar (mass median aerodynamic diameter (MMAD) 3.7 and 3.8 microns; geometric standard deviation (GSD) 1.8 and 1.5 for the hypo- and hypertonic aerosols, respectively). The present results confirm the effects of tonicity on deposition of aerosols found in a parallel study reported in this issue of the Journal. They also give support to the theory that, in addition to the concentration of the nebulized solutions, the number of droplets per volume of the carrier air is a factor affecting deposition of aqueous aerosols. The presence of 0.5% nedocromil sodium in the solutions did not appear to interfere with the processes of heat and water transfer in the airways.

Adult↗
PubMed1993

Kappa immunoglobulin promoters and enhancers display developmentally controlled interactions.

We have investigated the interaction of the kappa immunoglobulin light chain intron and 3' enhancers with two different kappa promoters at distinct stages of B-cell development. We find that transiently transfected reporter gene constructs driven by either the kappa V-region promoter, or the kappa germline promoter, are controlled by the known enhancers of the locus in a developmentally regulated fashion. We have, however, observed differences in promoter activation by each enhancer. Moreover, constructs controlled by a combination of both enhancers are synergistically activated at the B-cell and plasma cell stages as compared with constructs containing either enhancer alone. This synergy is not observed early in development, at the pre-B cell stage. The pattern of enhancer and promoter interactions is discussed in the context of the known developmental regulation of the locus.

Animals↗
PubMed1993

A common proviral integration region, fit-1, in T-cell tumors induced by myc-containing feline leukemia viruses.

Feline leukemia viruses carrying transduced v-myc genes (myc-FeLV) induce tumors of clonal origin, suggesting that activated myc alone is not sufficient for tumorigenesis. To investigate the hypothesis that insertional mutagenesis plays a role by activating genes which collaborate with v-myc, we looked for evidence of common proviral integration sites in these tumors. By inverse polymerase chain reaction we identified a 6-kb domain, designated fit-1, in which FeLV proviruses were inserted in four of nine (44%) T-cell tumors induced by myc-FeLV. The fit-1 locus was mapped to feline chromosome B2 and appears to be distinct from known oncogenes located on this chromosome. Fit-1 represents a novel common proviral integration region which may harbor a cellular gene which acts in concert with the myc gene in T-cell tumorigenesis.

Animals↗
PubMed1993

Coincident involvement of flvi-2, c-myc, and novel env genes in natural and experimental lymphosarcomas induced by feline leukemia virus.

The flvi-2 locus is a target of insertional mutagenesis in thymic lymphosarcomas induced by feline leukemia virus (FeLV). flvi-2 encodes the gene bmi-1, whose product is implicated as a myc-collaborator in the induction of B- and T-cell lymphoma. We have examined the involvement of flvi-2 and myc in natural and experimentally induced FeLV-positive feline lymphosarcomas which are heterogeneous in anatomical origin, geographic origin, and strain of FeLV involved. We further compared these findings with previous reports of novel FeLV env genes in the same tumors. The results show that proviral insertion at flvi-2 occurs commonly in natural and experimental feline thymic lymphosarcomas of diverse origins [52% overall], and that alterations in c-myc commonly accompany insertional mutagenesis of flvi-2 [54% overall]. However, 46% of tumors with flvi-2 insertions apparently lack involvement of c-myc. These observations support the hypothesis that interruption of flvi-2 may be an early event in a multistep cascade, one possibility for completion of which is activation of c-myc. Interruption of flvi-2 was not observed in nonthymic lymphosarcomas of alimentary or multicentric origin, although c-myc may be involved. A proportion of both thymic and nonthymic tumors have been shown previously to contain FeLV proviruses with recombinant or mutant env genes. Our findings strongly implicate the insertional mutagenesis of flvi-2, the activation of c-myc, and the emergence of novel env genes in FeLV-mediated lymphomagenesis, particularly in the induction of thymic lymphosarcoma. The data show that these events may overlap, but do not necessarily occur concurrently.

Animals↗