Biomedical subjects

S Arrigo

Publications and source records attributed to S Arrigo.

7 recordsLinked to original sources

PubMed1998

SCID mice with HIV encephalitis develop behavioral abnormalities.

Severe combined immunodeficient (SCID) mice inoculated intracerebrally (i.c.) with HIV-infected human monocytes develop brain pathology similar to that in humans with HIV encephalitis. This includes HIV-positive macrophages and multinucleated giant cells, astrogliosis, microglial nodules, and neuronal dropout. These xenografts survive about 1 month. To develop a model of chronic HIV encephalitis and to assay the resulting behavioral abnormalities, we reinoculated SCID mice i.c. every 4 weeks for 3 months with either HIV-infected human monocytes (n = 5) or uninfected human macrophages (n = 4) or administered no inoculation (n = 6); these three groups were monitored for behavioral abnormalities. Tests of cognitive function in a Morris water maze 3.5 months after the first inoculation suggested that HIV-infected mice performed poorly compared with controls. Following testing in the water maze on days 4 and 5 of acquisition, motor activity of infected mice was reduced in comparison with that of controls. Retention of goal location when tested 1 week later was impaired in HIV-infected mice compared with controls. Histopathologic analysis of brains revealed significant astrogliosis and strongly suggested higher numbers of major histocompatibility complex (MHC) class II-positive multinucleated macrophages in HIV-infected compared with control mice. Thus, our preliminary studies indicate that SCID mice with HIV encephalitis develop behavioral abnormalities reminiscent of human disease. These behavioral abnormalities are associated with significantly increased astrogliosis, the presence of HIV, and probably multinucleated giant cells. These studies further support the use of this SCID animal model system for studies of the pathogenesis of HIV encephalitis and for drug interventions.

AIDS Dementia Complex↗

PubMed1996

On-line urea kinetics in haemodiafiltration.

BACKGROUND: Calculation of Kt/V and assessment of nutrition have so far been dependent upon off-line urea measurements of blood or dialysate samples. Here we describe a biosensor for on-line urea measurement during haemodiafiltration. Methods. The biosensor consisted of a cartridge containing covalently linked urease placed between two conductivity cells. The biosensor was placed on the outlet line of a haemofilter in series with a dialyser in order to obtain an aliquot of plasma ultrafiltrate for on-line measurement of urea. RESULTS: Urea nitrogen concentrations were highly correlated to the difference (Delta) in conductivity measured by the two conductivity cells both in aqueous solutions (in-vitro studies, y=-6. 676+32.12x, R2=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies, y=-637+32.01x, R2=0.98, P<0.00001). Delta conductivity was highly reproducible (% variation: ).8-5.3%) and stable (maximal % variation at 150 mg/dl after 100 min. 0.9+/-0.3 vs initial values). The intradialytic plasma water urea profile was obtained in 10 haemodialysis patients. To study recirculation, the plasma water urea profile was analysed before and 3 min after stopping the dialysate flow. The pre- and post-stopped flow ratio (1.21+/-0.1, mean+/-1 SD) was superimposable to conventional blood sampling data (opposite arm venous arterial: 1.22+/-0.11) and allowed correction for recirculation. A novel approach to urea kinetic modelling was described and used to reliably project end-dialysis and post-dialysis rebound urea concentration as early as 90 min. Projected (29.2+/-10.4 g) or measured (29.8+/-10.5 g) net urea removal was highly correlated with the amount of urea collected in the total spent dialysate (29.7+/-10.6 g) (R2=0.99, R2=0.97 respectively). CONCLUSIONS: These results indicate that on-line, real-time analysis of urea kinetics may provide information on delivery of adequate dialysis in high-efficiency techniques.

Adult↗

PubMed1991

Regulation of HTLV-II gene expression by Rex involves positive and negative cis-acting elements in the 5'long terminal repeat.

Regulation of human T-cell leukemia virus type II (HTLV-II) gene expression by the trans-acting viral protein, Rex, is mediated through specific cis-acting sequences in the HTLV-II long terminal repeat (LTR). Augmentation of 5' LTR-linked gene expression by Rex requires two distinct cis-acting elements: one termed the "Rex-responsive element" (RxRE), which allows Rex to overcome the inhibitory effect of a second, termed the "cis-acting repressive sequences" (CRS). The HTLV-II RxRE is located between nt +91 and +317 relative to the cap site in the R/U5 region of the 5'LTR, and the HTLV-II CRS is contained within the RxRE from nt +208 to +317, which is downstream of the splice donor site, in the R/U5 region of the 5' LTR. Deletion of the CRS results in significantly increased cytoplasmic levels of LTR-linked mRNA independent of the presence of Rex. Our results show that Rex acts post-transcriptionally and induces a shift from nucleus to cytoplasm of gag/pol mRNA, the only HTLV-II mRNA that contains both the RxRE and the CRS in the 5' LTR-derived leader sequence.

Base Sequence↗

PubMed1990

Better survival after combined modality care for adults with Wilms' tumor. A report from the National Wilms' Tumor Study.

Adults with Wilms' tumor (WT) have had a poor prognosis. More recently, therapies used in children, who have a better outlook, are also being employed for adults. This study was undertaken to see whether adults with WT have benefited. The results of treatment of 27 adults with WT were reported to the National Wilms' Tumor Study (NWTS) from 1979 to 1987. The ages of the 27 adults ranged from 16 to 74 years (median, 24 years). Four had anaplastic WT, and 23 had favorable histology (FH) WT. All but one patient underwent nephrectomy, 21 were given postoperative radiation therapy, and 25 received chemotherapy. The agents used most often included actinomycin D (AMD), vincristine (VCR), and doxorubicin (Adriamycin; ADR). There were six Stage I, five Stage II, four Stage III, 11 Stage IV, and one Stage V patients. The 3-year survival rate is 67%. These results are better than the 24% reported by the NWTS in the past for adults with WT. Analyses of the therapies given to the 27 adults lead to the following recommendations: for Stage I/FH patients, 6 months of postoperative chemotherapy using AMD + VCR without postoperative radiation therapy; and for Stage II, III, and IV/FH, VCR + AMD + ADR for 15 months + 2000 cGy to the tumor bed, 1200 to 1500 cGy to the lungs, 2000 cGy to the liver, and 3000 cGy to other sites as appropriate in patients with metastases at diagnosis.

Adolescent↗

PubMed1988

Regulation of Rous sarcoma virus RNA splicing and stability.

Only a fraction of retroviral primary transcripts are spliced to subgenomic mRNAs; the unspliced transcripts are transported to the cytoplasm for packaging into virions and for translation of the gag and pol genes. We identified cis-acting sequences within the gag gene of Rous sarcoma virus (RSV) which negatively regulate splicing in vivo. Mutations were generated downstream of the splice donor (base 397) in the intron of a proviral clone of RSV. Deletion of bases 708 to 800 or 874 to 987 resulted in a large increase in the level of spliced RSV RNA relative to unspliced RSV RNA. This negative regulator of splicing (nrs) also inhibited splicing of a heterologous splice donor and acceptor pair when inserted into the intron. The nrs element did not affect the level of spliced RNA by increasing the rate of transport of the unspliced RNA to the cytoplasm but interfered more directly with splicing. To investigate the possible role of gag proteins in splicing, we studied constructs carrying frameshift mutations in the gag gene. While these mutations, which caused premature termination of gag translation, did not affect the level of spliced RSV RNA, they resulted in a large decrease in the accumulation of unspliced RNA in the cytoplasm.

Avian Sarcoma Viruses↗

PubMed1987

cis-acting regulatory elements within gag genes of avian retroviruses.

A cis-acting enhancer element has been detected within the gag gene of several avian retroviruses, including Rous sarcoma virus, Fujinami sarcoma virus, and the endogenous Rous-associated virus-0. A consensus enhancer core sequence, GTGGTTTG, is present in all of these viral genomes, approximately 900 bases downstream from the site of initiation of transcription. When an internal fragment derived from the gag gene of any of these viruses (spanning nucleotides 533 to approximately 1149) was inserted into a plasmid containing the chloramphenicol acetyltransferase (cat) gene under control of the simian virus 40 promoter, 9- or 21-fold enhancement of CAT expression was observed after transfection into mouse L cells and chicken embryo fibroblasts, respectively. This enhancement was not dependent on the position of insertion of the gag fragment into the plasmid. However, there was a strong dependence on orientation, with higher levels of CAT expression in constructs in which the 5' end of the gag fragment was nearest to the promoter, suggesting a possible negative regulatory element at the 3' end of this fragment. Deletion of the 3' end of the insert resulted in a gag fragment, containing nucleotides 533 to 1017, which enhanced expression equally in either orientation. When the gag fragment was inserted into a plasmid containing the cat gene under the control of an intact Rous sarcoma virus long terminal repeat, it induced a two- to threefold increase in CAT activity and CAT mRNA levels. Translation of the gag fragment did not appear to be necessary for the observed enhancement, since two insertional mutations resulting in frameshifts in the gag insert did not affect CAT expression. However, deletion of a 330-base internal fragment from the gag insert restored a basal level of CAT activity. These results suggest that retroviruses have regulatory elements within their genes distinct from those in the long terminal repeats that flank the genes.

Animals↗

PubMedDate not supplied

Early lung function changes after short heavy exposure to chrysotile asbestos in non-smoking women.

Forced spirometry, including maximal flow-volume (MEFV) curves, were evaluated in 35 non-smoking asbestos female workers submitted to a short heavy chrysotile textile exposure and compared to a case by case matched population. Exposed women presented certain respiratory signs and symptoms; they also had significantly lower forced vital capacities and maximal flow rates at higher (PEF), mid (MEF50%) and lower lung volumes (MEF25%) than women not exposed to asbestos. Duration of exposure to asbestos showed a significant negative correlation with FVC, FEV1, PEF, MEF50% and MEF25%. It is concluded that short heavy exposure to chrysotile is deleterious, causing significant reduction in lung volumes. Moreover, a significant reduction in airflow rates was also apparent.

Adult↗