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Biomedical subjects

S L Abreu

Publications and source records attributed to S L Abreu.

At least 19 recordsLinked to original sources
PubMed1986

Interferon in experimental autoimmune encephalomyelitis: intraventricular administration.

Highly purified rat fibroblast-derived interferon (RfIFN), was administered intraventricularly to Lewis rats affected with experimental autoimmune encephalomyelitis (EAE). Its effects on both the active and passive forms of EAE were studied. A method was devised to deliver, via a syringe pump, RfIFN (sp. act. 10(8) U/mg) into the third ventricle of control and experimental animals. Rats with either the active form of EAE (produced by injection with myelin basic protein (MBP) in Freund's complete adjuvant) or with adoptively transferred EAE were treated with RfIFN either therapeutically and/or prophylactically. In no instance was a significant difference observed, on the course of EAE, between those animals receiving RfIFN and those receiving "mock" IFN. The pharmacokinetics of the infused RfIFN were also studied.

Animals↗
PubMed1986

Adoptive transfer of allergic encephalomyelitis by inoculation of cells into lymph nodes.

Experimental allergic encephalomyelitis can be transferred passively by lymph node cells from actively immunized donor rats to immunologically naive syngeneic recipients. In the present work, passive transfer was accomplished by direct inoculation of donor cells into the recipient's lymph node, and this route was more effective than the conventional intravenous or intraperitoneal routes.

Animals↗
PubMed1985

The acquisition of encephalitogenicity after sensitized cells are conditioned with myelin basic protein or concanavalin A.

When cells from rats immunized against neural antigens are incubated with myelin basic protein or concanavalin A, their ability to transfer experimental allergic encephalomyelitis (EAE) is greatly increased. Using the rapid, localized form of EAE, we have shown that the increased encephalitogenicity of these cells was not manifest, or not fully manifest, in 1 day after passive transfer. Expression of the increased encephalitogenic potency required a period of residence in the recipient animal and this period did not depend on the duration of incubation in vitro. Conditioned cells were fully capable of eliciting the neutrophilic form of EAE, which is consistent with the notion that the recipient's mononuclear cells were not essential for the expression of the encephalitogenic potential of conditioned donor cells.

Animals↗
PubMed1985

A high-yield chromatographic method for the purification of rat fibroblast interferon to a high specific activity.

Rat fibroblast interferon (RfIFN), produced in serum-free media, has been purified 2,000-fold to 88% purity by a simple method that involves only two chromatographic steps: controlled pore glass and phenyl agarose chromatography. Over 70% of the initial activity was recovered. Gel electrophoresis (SDS-PAGE) and silver staining of the purified RfIFN revealed two major bands of RfIFN activity corresponding to Mr of 26,000 and 22,500 daltons, respectively. A very small amount of RfIFN was also recovered from a region of the gel corresponding to a Mr of 18,500. The average specific activity of the purified material was 3.7 X 10(8) U/mg. From these results it can be calculated that the specific activity of homogenous RfIFN is 4.0 X 10(8) U/mg.

Animals↗
PubMed1985

Interferon in experimental autoimmune encephalomyelitis (EAE): effects of exogeneous interferon on the antigen-enhanced adoptive transfer of EAE.

The transfer of experimental autoimmune encephalomyelitis (EAE) can be enhanced by incubating lymph node cells (LNC) from EAE rats with myelin basic protein (MBP). Addition of rat fibroblast interferon (RfIFN) to cultures of EAE-LNC just before the addition of MBP, resulted in the inhibition of the adoptive transfer of EAE. Both development of clinical signs, such as weight loss and hind limb paralysis, and histopathological lesions, lymphocytic perivascular infiltrates of the central nervous system, were inhibited by the addition of RfIFN to a final concentration of 300 U/ml or higher. This inhibition was dose dependent and appeared to be mediated primarily by the antiproliferative action of RfIFN.

Animals↗
PubMed1984

Rat fibroblast-derived interferon: production in serum-free medium and enhancement by theophylline.

Incubation of rat fibroblasts (RFA-1) with theophylline after Newcastle disease virus (NDV) induction, increased rat fibroblast interferon (RfIFN) yields 3 to 10-fold. However, incubation with butyric acid for 24 or 48 h before NDV addition resulted in no change or decrease in IFN production. Combined treatment with butyric acid and theophylline did not improve the yields obtained with the methylxanthine alone. Production of IFN by RFA-1 cells was the same in serum-free and in serum-containing media. These findings will facilitate RfIFN production and purification.

Animals↗
PubMed1983

Suppression of experimental allergic encephalomyelitis by tilorone: cell transfer and interferon studies.

Tilorone is known to induce interferon and to suppress experimental allergic encephalomyelitis (EAE) produced by active immunization. In the present work, tilorone was given to donors or recipients of the passive transfer form of EAE, using a localized variety of 1 or 4 days duration and a nonlocalized form of 8 days duration. The results indicated that tilorone inhibited EAE by retarding the clonal expansion in response to antigen, by a reversible inhibition of EAE effector cells, and probably by an effect on nonspecific reactive cells in the perivascular inflammatory infiltrates. Inhibition of EAE was not mediated by the induction of interferon, but was associated with depletion of T lymphocytes.

Animals↗
PubMed1983

Inhibition of passive localized experimental allergic encephalomyelitis by interferon.

Recently it has been reported that interferon (IFN) suppresses experimental allergic encephalomyelitis (EAE) in actively immunized Lewis rats. In the present study the effect of IFN on a localized form of passively transferred EAE has been investigated. Localization and acceleration of the disease was obtained by injection of EAE lymph node cells into rats which had, 3 days previously, been prepared with a thermal brain injury. Within 24 h of cell transfer perivenular lymphocytic infiltrates (EAE lesions) were observed in the brain. Administration of IFN (40,000 U/kg) right after EAE lymph node cell injection resulted in a significant reduction or elimination of EAE lesions. The possibility that IFN is acting exclusively on the afferent arc is eliminated, and the results suggest that IFN may be acting, although not solely, through modulations of components of the efferent arc. IFN was equally effective in suppressing EAE in adrenalectomized animals. This demonstrates that the immunosuppressive effects observed in this study are not due to endogenously produced corticosteroids.

Adrenalectomy↗
PubMed1983

Pharmacokinetics of rat fibroblast interferon.

The pharmacokinetics and tissue distribution of rat fibroblast interferon (RfIFN) after i.v., i.p. and i.m. administration were studied. RfIFN i.v. administered into Lewis rats was rapidly cleared from the blood with a half-life of about 10 min during the 1st hr. After 1 hr, clearance was slower. Intraperitoneal- and i.m.-injected RfIFN showed peak serum levels 1 hr after injection. Serum levels after i.m. administration were lower than after i.p. injection. However, no RfIFN was detected in the blood 24 hr after injection by any of these three routes. The injected RfIFN was found in kidney, liver, spleen and lung, but RfIFN levels were 3 to 10 times higher in the kidney than in any other organ. No RfIFN was found in the urine. Very low levels of RfIFN were found in the cerebrospinal fluid of normal rats. In rats with active experimental allergic encephalomyelitis, the amount of RfIFN in the cerebrospinal fluid was small but 3 times higher than in normal rats. No RfIFN was found in the brain tissue of normal or experimental allergic encephalomyelitis rats.

Animals↗
PubMed1982

rRNA accumulation and protein synthetic patterns in growing mouse oocytes.

The rRNA contents of mouse primordial oocytes, three stages of growing oocytes, full-grown oocytes, and ovulated ova have been measured by hybridization of RNA samples to excess 3H-DNA complementary to rRNA. Since it was known from previous work that rRNA is stable, the results when plotted against days of oocyte growth indicated that rRNA was synthesized at a constant rate over the first 9 days of growth and about 1.5 times faster in the last 5 days. The maximum value of 0.3 ng per oocyte was attained by about 14 days of growth in oocytes 59 micrometers in diameter, well below the maximum diameter of 77 micrometers for full-grown oocytes. The stability of proteins synthesized in mid-growth phase oocytes was measured by labeling for 5 h with 35S-methionine and then following the decline of incorporated label during a 48h chase; 40% of the label decayed with a half-life of 11 h. and 60% was apparently stable. The two-dimensional electrophoretic patterns of labeled proteins synthesized by growing and full-grown oocytes were compared. The principal change was the appearance or great increase in intensity of several spots in full-grown oocytes as compared to growing oocytes. Egg proteins separated on a two-dimensional gel were visualized by silver staining. The cytoskeletal proteins actin, tubulin, and putative intermediate filament protein, as well as putative lactate dehydrogenase, were synthesized in growing and full-grown oocytes, and accumulated to form a significant portion of bulk egg protein.

Animals↗
PubMed1982

Suppression of experimental allergic encephalomyelitis by interferon.

Experimental allergic encephalomyelitis (EAE) is an experimental, T-cell dependent, autoimmune disease of the central nervous system that can be induced in most mammals by the injection of myelinated neural tissue in complete Freund's adjuvant. Relatively small doses, 10(4.6) Units/kg, of rat interferon (IFN), specific activity 10(7.6) Units/kg, delayed the onset of the disease and significantly ameliorated the severity of EAE symptoms observed in Lewis rats. Injection of IFN at 10(5.6) U/Kg suppressed hind limb paralysis in 70 to 80% of the rats.

Animals↗
PubMed1982

Characterization of a new, continuous rat fibroblast cell line, RFA-1: a high producer of interferon.

A new continuous rat fibroblast cell line (RFA-1) was characterized and its interferon (IFN) production and sensitivity to IFN compared with eight rat cell lines. After 95 passages, and about 380 population doublings, these cells exhibited chromosomal heterogeneity, but 55% still possessed the diploid chromosome number of 42. RFA-1 grown in Dulbecco's modified Eagle's medium-10% calf serum have a doubling time of 17.2 h and a saturation density of 141,487 cells/cm2. The geometric mean IFN production by these cells was 10(3.8) U/ml, and this was at least 10(0.5) U/ml higher than IFN production by the second highest IFN producer. Similarly, RFA-1 cells were at least three times more sensitive to the protective effects of interferon against vesicular stomatitis virus-induced cytopathic effects.

Animals↗
PubMed1981

Induction and cross-species activity of rat fibroblast-derived interferon.

Interferon derived from rat fibroblasts (RFA-1) was pH 2 stable and heat labile. Denaturants such as SDS and urea inactivated this interferon but beta-mercaptoethanol alone did not. IFN yield after Newcastle disease virus was multiplicity of infection (moi) dependent. Optimal induction was obtained with an moi of 10. RFA-1 cells produced small amounts of IFN (less than or equal to 10(1.5) U/ml) when exposed to varying amounts of poly(rI): poly(rC). Addition of DEAE-dextran and/or pretreatment with IFN did not change this response. Pretreatment resulted in increased interferon production, priming, but on the average it was only about a 2-fold increase. However, the kinetics of interferon production were altered by pretreatment with IFN whether there was an increase in production or not. Both IFN synthesis and production peaks were detected 2-4 h earlier in IFN-pretreated RFA-1 cells. Rat IFN exhibited a great deal of cross-species activity. It is 100-300% cross-reactive on mouse (L929B and 3T3) cells, and 5-10% active on guinea pig fibroblasts, human (GM 2767) and bovine (MDBK) cells. These cells were more sensitive to rat IFN than Jensen sarcoma cells (a rat tumour cell line). Neither chicken embryo fibroblasts nor monkey (Vero) cells developed an antiviral state when exposed to rat IFN.

Animals↗
PubMed1979

Interferon priming. Effects on interferon messenger RNA.

The effects of priming mouse cells with interferon on the production of interferon and its mRNA were investigated. Interferon-treated (primed) mouse L929 cells produce 3 to 10 times more interferon than do nonprimed cells following induction with Newcastle disease virus. Interferon appears 2 to 4 h sooner in the primed cultures than in nonprimed cultures and interferon production by primed cells becomes resistant to inhibition by actinomycin D about 4 h sooner than interferon production in nonprimed cells. Interferon mRNA is detected in primed-induced cells about 2 h earlier than in nonprimed-induced cells. It reaches peak levels about 2 to 4 earlier in primed cells, but it also disappears sooner in primed cells. The total amounts of interferon mRNA isolated from primed-induced cells and nonprimed-induced cells were indistinguishable, by the methods utilized. Therefore, although primed cells can produce significantly more interferon and make interferon mRNA sooner than nonprimed cells, the total amount of interferon mRNA produced is apparently not increased, nor is its half-life prolonged in primed cells. Thus, enhanced interferon production in primed cells may result from enhanced efficiency of translation of interferon mRNA in the primed cells.

Animals↗
PubMed1979

Production, purification and characterization of rat interferon.

Priming with heterologous mouse interferon, increased production of an antiviral substance induced in rat diploid fibroblasts by Newcastle disease virus. This substance was characterized as an acid stable interferon. This rat interferon exhibited marked cross-species antiviral activity when tested in mouse L929B cells, guinea pig embryo fibroblasts, human fibroblasts and bovine cells but was not active on chick embryo cells.

Animals↗