A recombinant feline leukemia virus (FeLV) proviral clone (T17T-22) with a long terminal repeat (LTR) which differs from prototype FeLV by a point mutation within a conserved nuclear factor 1 (NF1)-binding motif in the LTR enhancer domain was found to be poorly expressed after DNA transfection. The NF1 point mutation reduced in vitro protein binding as assessed by gel shift analysis and reduced promoter activity significantly (2- to 10-fold). However, the degree of promoter impairment due to the NF1 site mutation varied according to cell type and was least severe in a feline leukemia cell line (T3) which had low levels of nuclear NF1 DNA-binding activity. Low NF1 DNA-binding activity was observed in three FeLV-induced leukemia cell lines (T3, T17, and FL74) and in murine F9 embryonal carcinoma cells. While similar levels of NF1 gene mRNA transcripts were detected in all cell lines, Western immunoblot analysis of F9, T17, and FL74 but not T3 nuclear extracts revealed very low levels of nuclear NF1 protein. These results indicate that NF1 activity is down-regulated in FeLV-induced leukemia cells by diverse posttranscriptional mechanisms. We suggest that NF1 down-regulation may be an important characteristic of target cells susceptible to FeLV transformation in vivo and may provide the selective pressure which favors duplication of the LTR core enhancer sequence in T-cell leukemogenic FeLV variants.

Animals↗

PubMed1991

Effect of recombinant human granulocyte colony-stimulating factor on hematopoiesis in normal cats.

The objective of this study was to determine how recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects hematopoiesis in normal cats. Recombinant human G-CSF was given at 3.0, 5.0, and 10.0 micrograms/kg to two cats each s.c. twice daily for 21 days. This resulted in significant (p less than 0.01) elevations of peripheral blood neutrophils from 3.0- to 9.2-fold above pretreatment levels and significantly (p less than 0.02) above levels of nontreated control cats (n = 4). A statistically significant dose-related response was not seen at these dosages in any parameter evaluated. The period of maximum neutrophilia occurred between days 10 and 14 of rhG-CSF treatment, with maximum neutrophil counts ranging from 20,370 cells/microliters to 61,400 cells/microliters (normal is less than 12,500). Lymphocytosis (greater than 7000 lymphocytes/microliters) and monocytosis (greater than 850 monocytes/microliters) were observed in 50% of the cats receiving rhG-CSF during the period of maximal neutrophil stimulation. Monocyte counts in treated cats were significantly (p less than 0.01) elevated over those of treatment controls on days 12-17. Lymphocyte numbers in rhG-CSF-treated cats were significantly elevated (p less than 0.05) over pretreatment controls on days 12 and 14 of rhG-CSF treatment. No significant changes were observed in reticulocyte counts, platelet counts, or hematocrit levels. By day 19, neutrophil levels had dropped significantly (p less than 0.01) from the maximum neutrophil levels, with one cat attaining a normal blood neutrophil count by day 21 of rhG-CSF treatment. Marrow aspirates revealed an overall increase in marrow cellularity through day 14 of treatment in rhG-CSF-treated cats, with increased myeloid:erythroid ratios (two- to ninefold) over those of nontreated controls. The erythroid and lymphoid component of the marrow decreased from day 0 to day 14, whereas the early myeloid progenitors (myeloblasts, progranulocytes, and myelocytes) increased significantly (p less than 0.05). No significant differences in the percentage of later myeloid forms in the marrow were observed over the treatment period. In vitro colony-forming assays of marrow obtained from treated cats revealed increases in granulocyte-macrophage colony-forming units (CFU-GM) through day 14, with subsequent decreases by day 21 of rhG-CSF treatment. Recombinant human G-CSF was also effective at in vitro stimulation of feline marrow cells from untreated cats in a dilution study, with maximal CFU-GM formation at 0.1 microgram rhG-CSF/ml assay.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Skin rash associated with accidental addition of excess aluminium sulphate to the water supply.

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Adult↗

PubMed1991

Effects of tracer blood measurement noise on glucose metabolic rate estimation.

Tracer kinetic modeling with Positron Emission Tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, computer simulations were performed to investigate the influence of input measurement noise on the accuracy of estimates. The results show that input measurement noise causes considerable variability in the parameter estimates.

Blood Glucose↗

PubMed1991

Restoration of neutrophil and platelet function in feline Chediak-Higashi syndrome by bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) was successfully performed in four Chediak-Higashi (CHS) syndrome affected cats. Preparatory regimens included selective intestinal flora decontamination, fractionated total body irradiation for myeloablation, and prophylactic treatment for graft-versus-host disease with cyclosporin A. Neutrophil chemotaxis under-agarose and whole-blood platelet aggregation/secretion were characterized prior to BMT and after engraftment of donor-origin marrow cells. Liver and kidney biopsies were obtained and evaluated by light and electron microscopy before, and at 6 months post-BMT to determine what effect BMT might have on abnormal lysosome fusion in hepatocytes and renal tubule cells. The platelet storage pool defect was resolved by day 40 post-BMT. In vitro neutrophil migration in all cats appeared to improve with time after BMT and complete restoration was evident by day 175 post-BMT. No apparent differences were evident in either the liver or the kidney at 6 months post-BMT. One cat developed seizures and one developed posterior paresis 5 months post-BMT; neurologic impairment ultimately resulted in death of two cats at 6 and 8 months post-BMT, respectively. Neurologic lesions in both cats were characterized by non-suppurative encephalitis. Allogeneic BMT successfully corrected the neutrophil migration defect and platelet storage pool deficiency but had no effect on lysosome distribution in liver and kidney cells of CHS cats.

Adenosine Triphosphate↗

PubMed1990