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Biomedical subjects

S M Russell

Publications and source records attributed to S M Russell.

At least 73 records · Page 4Linked to original sources
PubMed1992

A rapid method for the determination of temperature abuse of fresh broiler chicken.

Ready-to-cook broiler chicken carcasses were obtained immediately postchill from a commercial processing plant. A control group was held at 4 C for 10 days. Test groups were held at 4 C for 2 days, temperature abused at 10, 15, or 20 C for 0, 1, 2, 4, 6, 8, 12, or 24 h, and then held at 4 C for an additional 4 days. Both control and test birds were sampled using whole carcass rinse techniques and bacteria enumerated using impedance detection times (DT) and total plate count (TPC) techniques at incubation temperatures of 18 and 42 C. The DT and TPC showed a significant increase (P less than .05) in the number of organisms recovered at 18 C but did not show a significant increase (P less than .05) in organisms recovered at 42 C when carcasses were held at 4 C continuously for up to 10 days. Carcasses that were temperature abused at 10 C for up to 24 h were not significantly different (P less than .05) from the unabused controls, using either DT or TPC, following incubation at 18 and 42 C. At an incubation temperature of 18 C, carcasses abused at 15 or 20 C had significantly more growth of bacteria than controls at 1, 6, 12, and 24 h and 4, 8, and 12 h as determined by DT and at 6, 12, and 24 h and 1, 2, 4, 8, and 12 h, respectively, as determined by TPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Alternatively spliced RNAs encode several isoforms of CD46 (MCP), a regulator of complement activation.

Five alternative cDNA clones were isolated for CD46, also known as the membrane cofactor protein (MCP) for the factor I-mediated cleavage of the complement convertases. One of these cDNA clones (a) was identical to an earlier MCP clone. The other four CD46 clones contained the four NH2-terminal short consensus repeat (SCR) units of MCP, but differed at the region encoding the carboxyl-terminal of the protein which includes an extracellular segment rich in Ser, Thr, and Pro residues, a hydrophobic membrane-spanning domain, and a 33 amino acid cytoplasmic tail. The different CD46 cDNAs have variously: (b) inserted a 93 base pair (bp) exon resulting in a new cytoplasmic tail of 26 amino acids; (c) deleted a 42 bp exon from the extracellular Ser/Thr rich region: (d) used a cryptic splice acceptor sequence to delete 37 bp from an exon encoding transmembrane sequence; or (e) failed to splice the intron after the four SCR units. These were shown by northern blot and polymerase chain reaction to arise by alternative splicing of CD46 RNA. Forms (a), (b), and (c) of CD46 RNA are common in placental RNA, but (d) was rare, and (e) was incompletely processed and therefore aberrant. The polymerase chain reaction (PCR) was used to map the sites of the intron/exon junctions and demonstrate further possible splice variants of CD46. The alternative RNAs for CD46 may correlate to the different isoforms of CD46 found in different tissues, tumors, and in serum.

Amino Acid Sequence↗
PubMed1991

Analysis of the role of hormones and growth factors in growth control and tissue differentiation using transplanted mammalian embryos and fetal structures.

Results obtained from our analyses of the role of hormones and growth factors in rat embryonic and fetal development are reviewed. Whole 10-day embryos or structures from 14-16-day fetuses (paws, intestines, reproductive tracts) were transplanted under the kidney capsule of syngeneic host rats of different age, sex, physiological state or level of nutrition. In intact hosts, fetal transplants grew almost as much as they would have if left in situ in the fetuses, and tissue differentiation in them was essentially normal. By contrast, growth of embryo transplants was severely depressed relative to their growth in utero, but tissue differentiation was only slightly retarded. Fetal paws grew equally well in female hosts widely diverging in age and growth rate. Thus, in such hosts growth of the fetal paw was highly independent of the growth rate of the hosts. In hosts in which growth was arrested or reduced by diabetes, hypophysectomy or food restriction, growth of paw transplants was impaired, but not as severely as that of the hosts themselves. Fetal skeletal structures were relatively independent of thyroid hormones (TH) for growth; TH dependence developed progressively postnatally. In pregnant hosts, fetal paw transplants grew as well during the first half of gestation as they did in virgin females. By contrast, during the second half of pregnancy and during both halves of the lactational period, growth of the transplants was significantly reduced. Host skeletal growth was also inhibited during late pregnancy and throughout lactation. The impaired growth during the second half of gestation was associated with a large reduction in serum IGF-I concentration and a resistance to the growth-promoting actions of GH. In the lactating hosts, serum IGF-I concentration returned almost to prepregnancy levels and the resistance to GH persisted, but at a reduced level. The direct effects of hormones, growth factors, and antibodies to them on growth and tissue differentiation in the transplants were assessed using infusion methods. Substances were infused into the renal artery of transplant-bearing kidneys via catheters attached to osmotic minipumps. The direct effects of insulin, GH, IGFs, basic FGF and EGF on transplant growth and tissue differentiation were evaluated. Insulin directly stimulated growth of transplants in diabetic hosts but GH did not have a direct effect in hypophysectomized rats. The growth-restorative effects of GH observed in hypophysectomized hosts were apparently mediated indirectly via IGF-I. Infused rat IGF-II (MSA) was more effective at stimulating growth of embryo transplants than was recombinant human IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Effect of tumor necrosis factor on the antitumor efficacy and toxicity of aminopterin-monoclonal antibody conjugates: parameters for optimization of therapy.

Immunoconjugates of monoclonal antibodies with drugs, isotopes, or toxins are currently being investigated for their therapeutic effect on tumors. However, all have problems of access of the immunoconjugate to the tumor, particularly with solid tumors. To address this problem, we have used aminopterin-monoclonal antibody (AMN-mAb) conjugates combines with murine tumor necrosis factor (mTNF-alpha), which is known to have specific effects on tumor vasculature. In a murine model, well-established tumors (measuring 1.0-1.4 cm in diameter) were either totally eradicated or considerably reduced in size with combined therapy--a greater effect than with either mTNF-alpha or AMN-mAb used alone. The mechanisms involved in the improved antitumor effect were investigated using in vitro assays, autoradiography, and biodistribution experiments. mTNF-alpha was found both to increase the cytotoxic activity of the conjugate in vitro and to increase in vivo tumor localization of mAb up to 5-fold. The timing of mTNF-alpha administration was crucial to effects on tumor localization; mTNF-alpha given with mAb caused the greatest increase in localization and mTNF-alpha given well before mAb decreased localization. mTNF-alpha also reduced the toxicity to mice of AMN-mAb depending on the timing of injection. These results indicate that mTNF-alpha has a useful role in potentiation of immunoconjugate therapy but shows the need for careful planning of the dose regimen.

Aminopterin↗
PubMed1990

Tumor localization by combinations of monoclonal antibodies in a new human colon carcinoma cell line (LIM1899).

One of the problems of in vivo diagnosis and therapy of tumors with monoclonal antibodies is their heterogeneity with respect to antigen expression, with some cells expressing no antigen and others being weakly or strongly positive. Selected mixtures of antibodies to different antigens are therefore likely to react with more cells than single antibodies and be more effective for imaging and therapy. With this in mind, we have examined a new human colon cancer cell line (LIM1899) which has a heterogeneous expression of several cell surface molecules: by flow cytometry 38% were carcinoembryonic antigen positive; 64%, human milk fat globule positive, and 73%, CD46 positive; 87% of tumor cells bound a mixture of all three antibodies in vitro. Some blocking of the binding of anti-human milk fat globule antibody by the anti-CD46 antibody was noted. LIM1899 was established as a xenograft in nude mice and in vivo biodistribution studies performed using antibodies alone or in combination. Mixtures of antibodies clearly showed a higher percentage of injected dose of antibody in the tumor than did single antibodies: one antibody gave 10%; two together, 17 to 21%; and all three together gave 29% of the injected dose in the tumor. Tumor:blood ratios were also superior for combinations of antibodies, provided that low doses of the antibodies were used; at higher doses the effect was lost. The study demonstrates that combinations of antibodies are better than single antibodies for localization, provided that the dose used is carefully selected.

Animals↗
PubMed1990

Comparison of in vitro cell binding characteristics of four monoclonal antibodies and their individual tumor localization properties in mice.

Although many antibodies are being used for imaging studies, it is not clear which in vitro properties of antibodies will best reflect their in vivo characteristics. The ability to correlate in vitro binding characteristics of monoclonal antibodies to tumor antigens with their in vivo localization characteristics, particularly with respect to tumor localization properties, is desirable for rapid selection of monoclonal antibodies with potential for clinical use. The in vitro binding characteristics of three monoclonal antibodies to the murine Ly-2.1 antigen and one to the Ly-3.1 antigen have been studied on cultured tumor cells bearing these antigens. The association and dissociation rate constants, apparent affinity, and immunoreactivity of each antibody in vitro were compared with their ability to localize the s.c. tumors from the same cell line growing in Ly-2.1-/Ly-3.1-mice. The antibody with the highest affinity and fastest association rate localized to tumor at the earliest time (16-20 h after injection) and had the highest percentage of the injected dose/g in the tumor (greater than 25%). The antibody with the lowest affinity showed significantly less localization to tumor cells, compared with the other three antibodies. The ranking of the antibodies by affinity agreed with the ranking in terms of their ability to localize to tumors, but the in vitro immunoreactivity of the antibodies, as measured by a cell binding assay, did not correlate with their tumor localization properties. Immunoscintigraphic studies did not precisely correlate with biodistribution data or in vitro binding characteristics, because tumors could be satisfactorily imaged with each antibody, although it was noted that the antibody with the highest affinity gave the best image. The results indicate that kinetic binding parameters and affinity of monoclonal antibodies may be useful in predicting their potential for tumor localization and that kinetics of association of antibodies in vitro may predict localization kinetics in vivo.

Animals↗
PubMed1990

Neutralization epitopes of human rhinovirus type 2.

Fourteen neutralizing monoclonal antibodies recognizing human rhinovirus (HRV) type 2 have been used to select a total of 51 virus escape mutants. Cross-resistance analysis of the mutants, together with RNA sequencing and identification of amino acid substitutions, have revealed three neutralization sites on the virus surface. Two of these appear to correspond to the NIm-IA and NIm-II sites described for HRV-type 14, although there are also substantial differences. The third site has not been described previously.

Amino Acids↗
PubMed1990

Growth-promoting properties of the internal milieu of pregnant and lactating rats.

The growth-promoting properties of the internal milieu of pregnant and lactating rats were investigated using transplanted whole rat embryos or fetal paws. When placed under the kidney capsule of intact nonpregnant hosts and incubated for 12 days, such transplants grow rapidly, and tissues differentiate normally. Thus they provide an accurate means of assessing the growth-promoting properties of the internal environment of host animals in different physiological states. Transplant growth during days 0-11 of pregnancy was similar to that observed in age-matched virgin control hosts during an equivalent 12-day period. However, growth of transplants was decreased by 40% in hosts during days 10-22 of pregnancy and by approximately 30% in hosts during days 1-13 or days 11-23 of lactation. Increase in tail length, which was used as an index of maternal skeletal growth, was reduced by 50% during the second half of pregnancy and the early and late periods of lactation compared with age-matched virgin females. No such inhibition was recorded during the first half of pregnancy. Compared with virgins, serum insulin-like growth factor I (IGF-I) levels were reduced by approximately 20% on days 6 and 10 of pregnancy, and by 63-66% during the second half of gestation. Serum IGF-I levels rose during lactation to reach prepregnancy levels by day 12, but a second decline occurred by day 18 postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Analysis of the role of basic fibroblast growth factor in growth and differentiation of transplanted fetal rat paws and intestines.

Paws and intestinal segments from 16-day-old rat fetuses were transplanted bilaterally under the kidney capsule of adult female hosts and grown there for different periods of time. The direct effects of an antiserum to bovine basic fibroblast growth factor (bFGF) and of recombinant bFGF on growth and tissue differentiation in the transplants were evaluated by infusing them into the right renal artery via a catheter attached to an osmotic minipump. Infusion of the antiserum into the right kidney of intact hosts for 6 or 10 days did not affect either growth of the paws or bone differentiation in them. By contrast, the anti-FGF serum significantly inhibited the growth of intestinal transplants and caused slight retardation of villus differentiation. We presume that this inhibition resulted from neutralization of the bFGF produced within the transplants, as infusion of nonimmune rabbit serum had no such effects on the intestinal segments. In hypophysectomized hosts growth of both types of transplants was greatly reduced, and tissue differentiation was retarded, presumably reflecting low serum insulin-like growth factor-I levels. Infusion of the recombinant bFGF (5 micrograms/rat.day) into the hypophysectomized hosts stimulated growth of the paws and promoted ossification of the phalanges, but not the carpals. Intestinal growth was not affected by bFGF, and villus development was not restored. These results indicate that fetal rat structures are differentially dependent on and responsive to bFGF for growth and differentiation. These findings, when considered in relation to our previous results with transplanted 10-day-old rat embryos, indicate that growth and tissue differentiation during the embryonic period of rat development are more dependent on bFGF than are these processes in the fetal period.

Animals↗
PubMed1990

Evidence for a role of the liver in the mammotrophic action of prolactin.

The possibility that the liver plays a role in the growth-promoting actions of PRL on the mammary lobuloalveolar (L-A) system was investigated using 6-week-old female rats. Chronic indwelling catheters were inserted into the external jugular vein (EJV) or the hepatic portal vein (HPV) and attached to osmotic minipumps, which were used to infuse pulses of ovine (o) PRL (4/day of 2 h each, total dose = 20 micrograms/day) for 14 days. The rats were hypophysectomized 2 days after catheterization, and given daily sc injections of estradiol + progesterone in oil (2 micrograms and 5 mg/day, respectively) plus twice daily ip injections of porcine GH (50 micrograms/injection) from days 2-13. They were killed on day 14. Controls received the sc and ip hormone injections but were given solvent infusion into the EJV or the HPV instead of oPRL. Infusion of the oPRL into the EJV did not promote mammary L-A growth more than did infusion of solvent into either the EJV or the HPV. By contrast, infusion of the same dose of the hormone into the HPV caused a significant stimulation of the L-A growth. Serum insulin-like growth factor-I (IGF-I) levels were measured by RIA in the rats given the same hormone injections with either intrahepatic infusion of solvent or oPRL, but terminated 7 days after the start of infusion. Intrahepatic delivery of oPRL was not more effective at elevating serum IGF-I concentrations than was the infusion of solvent. These results indicate that the liver may participate in the mammotrophic actions of PRL and serum IGF-I is not responsible for this effect.

Animals↗
PubMed1990

Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. II. Protection from influenza infection and mechanism of protection.

Protection against influenza A virus infection in mice immunized with recombinant nucleoprotein (rNP) was studied. Nucleoprotein-immune mice were protected against a lethal challenge with A/Puerto Rico/8/34 (A/PR8) virus but showed considerable morbidity before recovery. Local boosting of the immune system with rNP by intranasal immunization improved the protection in NP-immune mice, and the decrease in morbidity after infection was reflected in accelerated clearance of virus from lungs. However, immune, boosted mice also rapidly cleared an antigenically unrelated influenza B virus from their lungs. Mice immunized with rNP precipitated with alhydrogel, that subsequently developed significant resistance to virus infection, failed to generate detectable levels of class I major histocompatibility complex (MHC)-restricted killer cells. Furthermore, B10.A(5R) mice that are non-responders for NP-specific class I killer cells could also be protected by immunization with rNP. In contrast, rNP-immunized mice developed strong proliferative T-cell responses to rNP. These data argue for an important role for helper T cells rather than virus-specific class I cytotoxic T cells in protection against influenza virus infection induced by rNP.

Animals↗