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Biomedical subjects

S M Russell

Publications and source records attributed to S M Russell.

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

The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor gamma chain as a common gamma chain, gamma c.

X-linked severe combined immunodeficiency is characterized by severe and persistent infections from early life resulting from profound impairment of both cellular and humoral immune function. XSCID is characterized by an absence or diminished number of T cells and histologic evidence of hypoplastic and abnormal differention of the thymic epithelium. The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes. This led to the speculation that IL-2R gamma would prove to be a common gamma chain, gamma c, which would play important roles in other cytokine receptors in addition to the IL-2 receptor. There is now compelling evidence to support a role in at least two other cytokine receptors, namely the IL-4 and IL-7 receptors. Thus, with inactivation of gamma c, multiple cytokine systems are simultaneously affected, resulting in the profoundly impaired phenotype of XSCID. It is possible and even likely that gamma c will be found to be a functional component of additional receptors as well. These findings have resulted in a significant improvement in our understanding of the pathophysiologic development of the defects in XSCID and also have important ramifications for prenatal and postnatal diagnosis, carrier female identification, and gene therapy for XSCID.

Animals↗
PubMed1994

Effect of freezing on the recovery of mesophilic bacteria from temperature-abused broiler chicken carcasses.

The effects of freezing on the recovery of mesophilic bacteria from broiler chicken carcasses were determined. Fifty fresh broiler carcasses were used in each of three independent trials. Ten carcasses were sampled at time of collection (Treatment 1: Day 0 control). The other 40 carcasses were sampled at Day 7 following one of four additional treatments with 10 carcasses each: held at 3 C (Treatment 2: 7-d control), frozen and then held at 3 C (Treatment 3: frozen control), temperature abused at 25 C for 12 h and held at 3 C (Treatment 4: temperature abused), and temperature abused at 25 C for 12 h, frozen, and held at 3 C (Treatment 5: temperature abused and frozen). Carcasses were sampled by rinsing, and total plate counts (TPC) expressed as log10 colony-forming units per milliliter and impedance detection times (DT) in hours were determined using incubation temperatures of 42 and 43 C, respectively. Results for TPC for Treatments 1 to 5 were 3.89, 3.52, 2.86, 6.53, and 5.57 log10 cfu/mL, respectively. Results for DT for Treatments 1 to 5 were 5.41, 6.50, 7.10, 2.55, and 3.42 log10 cfu/mL, respectively. Freezing reduced the ability to detect temperature abuse because of a significant reduction in the number of mesophiles recovered using either microbiological technique. Freezing appears to decrease, but may not completely eliminate, the ability of selective incubation to detect temperature abuse.

Animals↗
PubMed1994

The effect of incubation temperature on recovery of mesophilic bacteria from broiler chicken carcasses subjected to temperature abuse.

The optimum temperature to recover mesophilic organisms from temperature-abused broiler chicken carcasses was determined. Twenty broiler carcasses were collected from a commercial processing plant in each of three trials. Ten carcasses were sampled immediately (Day 0 control); 8 carcasses were sampled after holding at 3 C for 3 d, temperature abusing at 25 C for 12 h, and holding them at 3 C for an additional 3 d (temperature abused); and the remaining 2 carcasses were sampled after holding at 3 C for 7 d (Day 7 control). Whole carcass rinses were analyzed using total aerobic plate counts (TPC) and impedimetric detection times (DT) at incubation temperatures of 41, 42, 43, and 44 C. Total plate counts decreased (P < .05) and DT increased (P < .05), at all incubation temperatures tested, for carcasses held under refrigeration (Day 7 control). This demonstrates that mesophilic bacteria, rather than psychrotrophic bacteria, are being enumerated, because psychrotrophs increase on chicken skin upon cold storage. Total plate count was greater (P < .05) and DT was significantly lower for temperature-abused vs Day 7 control birds (5.7 vs 3.6 log10 cfu/mL and 3.7 vs 6.5 h), respectively. These results indicate that temperature-abused carcasses can be microbiologically distinguished from nonabused controls at all incubation temperatures tested. Recovery of mesophiles was optimal at 41 and 42 C for TPC and 41, 42, and 43 C for DT. Because there were no differences between DT at 41, 42, and 43 C, and because 42 C has been successfully used in the past, either 42 C or 43 C can be used when determining DT.

Animals↗
PubMed1993

Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor.

The interleukin-2 receptor gamma chain (IL-2R gamma) is a necessary component of functional IL-2 receptors. IL-2R gamma mutations result in X-linked severe combined immunodeficiency (XSCID) in humans, a disease characterized by the presence of few or no T cells. In contrast, SCID patients with IL-2 deficiency and IL-2-deficient mice have normal numbers of T cells, suggesting that IL-2R gamma is part of more than one cytokine receptor. By using chemical cross-linking, IL-2R gamma was shown to be physically associated with the IL-7 receptor. The presence of IL-2R gamma augmented both IL-7 binding affinity and the efficiency of internalization of IL-7. These findings may help explain the defects of XSCID. Given its role in more than one cytokine receptor system, the common gamma chain (gamma c) is proposed as the designation for IL-2R gamma.

Animals↗
PubMed1993

Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor.

The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is an essential component of high- and intermediate-affinity IL-2 receptors. IL-2R gamma was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2R gamma to augment IL-4 binding affinity, and the requirement for IL-2R gamma in IL-4-mediated phosphorylation of insulin receptor substrate-1. The observation that IL-2R gamma is a functional component of the IL-4 receptor, together with the finding that IL-2R gamma associates with the IL-7 receptor, begins to elucidate why deficiency of this common gamma chain (gamma c) has a profound effect on lymphoid function and development, as seen in X-linked severe combined immunodeficiency.

Animals↗
PubMed1993

Polymorphic expression of CD46 protein isoforms due to tissue-specific RNA splicing.

CD46 is a member of the regulators of complement activation (RCA) family and serves to protect autologous cells from complement mediated lysis. The CD46 gene consists of 14 exons and extensive RNA splicing produces protein isoforms of different molecular weight. Predominant protein isoforms of 66 and 56 kDa arise from splicing in or out of exon 8 which encodes a region rich in serine, threonine and proline residues known to be heavily O-glycosylated. An inherited allelic polymorphism controls the relative expression of these isoforms in PBL and other tissues. This study has analysed an independent and overriding tissue specific regulation of CD46 splicing. Salivary gland and kidney produce RNA transcripts that preferentially include exon 8, giving rise to the 66 kDa protein species, while exon 8 is spliced out in brain tissue to give the 56 kDa protein. The cytoplasmic tail of CD46 is encoded by either exon 13 (CYT 1) or exon 14 (CYT 2). There is a preferential deletion of exon 13 from transcripts in salivary gland, kidney and brain to encode a protein containing cytoplasmic tail CYT 2. This preferential production of the CYT 2 tail is contrary to that seen on peripheral blood lymphocytes where equivalent expression of both CYT 1 and CYT 2 is observed. Our results suggest that while the splicing of exons within most cells is controlled by nucleotide sequences within or close to the CD46 gene (i.e. cis-regulation), splicing in tissues such as salivary gland, kidney and brain is regulated by trans-splicing factors encoded by another gene(s).

Alternative Splicing↗
PubMed1993

Different membrane cofactor protein (CD46) isoforms protect transfected cells against antibody and complement mediated lysis.

The need for organ transplantation, especially of kidneys, exceeds the availability of human donors and the possibility of xenotransplantation from suitable animals is now being addressed. The immediate barrier to success is hyperacute graft rejection, resulting from naturally occurring xenoreactive antibodies and the activation of complement. It is proposed that the intensity of the hyperacute response can be reduced by providing additional regulatory molecules to limit activation of the complement cascade, initially as transfected gene products in cultured cells as an in vitro model and eventually as a transgene in potential donor animals, such as pigs. Limiting the activity of C3b reduces the production of the C3a, C4a and C5a anaphylotoxins, thus curtailing not only the immediate C3b-mediated lytic pathway but also the later effects of a cellular inflammatory response including endothelial and platelet cell activation. To develop and assess the first part of this strategy, we have transfected several cDNA's encoding isoforms of CD46 (membrane cofactor protein). At least four different CD46 isoforms are commonly expressed in almost all human cells, and we have compared two of these and a third form to determine if they mediate different functions. After transfection, CD46-expressing CHO-K1 cells were selected with methionine sulphoximine and identified using monoclonal antibodies. Transfectants with suitable CD46 expression were assayed for primary CD46 function using a lysis assay dependent on the reaction of antibody and complement. In this in vitro model of hyperacute rejection, normal human sera containing natural xenoreactive antibodies were shown to lyse CHO cells, but only in the presence of complement.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

An insulin-like growth factor I-resistant state in cartilage of diabetic rats is ameliorated by hypophysectomy. Possible role of metabolism.

This study investigated the effect of IDDM on cartilage anabolic activity in rats. Rats were injected with STZ to induce IDDM, were hypophysectomized, or were injected with STZ and hypophysectomized. After 14 days, control (intact and sham-Hx) and Hx rats were normoglycemic, whereas the rats with IDDM exhibited hyperglycemia and glycosuria. The HxDb rats, however, had normal blood glucose levels and no glycosuria. Both growth, serum levels of IGF-I, and basal cartilage 35SO4 incorporation measured in vitro were decreased in the Hx, IDDM, and HxDb groups. IGF-I added in vitro significantly stimulated 35SO4 incorporation by cartilage explants from control and Hx animals, whereas explants from the animals with IDDM were unresponsive. Explants from the HxDb rats, however, were stimulated by IGF-I in a dose-related manner. Because Hx corrected the glycemic status of the IDDM rats and restored cartilage responsiveness to IGF-I, a second set of experiments was undertaken to further investigate the relationship between cellular metabolism and anabolic activity in cartilage. Cartilage explants from rats fasted for 48 h showed significantly decreased basal 35SO4 incorporation, which was as low as that in explants from rats with severe IDDM. Whereas explants from the IDDM rats were completely unresponsive, those from the fasted rats (and fed rats) were significantly stimulated by the added IGF-I. However, incubation in the presence of 2-D-G, which causes intracellular glucopenia, or in the absence of glucose, completely blocked the anabolic response to IGF-I in otherwise responsive tissues. In conclusion, an important component of diabetic growth inhibition appears to be tissue resistance to the anabolic action of IGF-I, a condition that is correctable by Hx and that may be a result of metabolic impairment at the tissue level.

Analysis of Variance↗
PubMed1993

Effect of lactic acid fermentation on bacterial pathogens and indicator organisms in broiler processing waste.

Broiler processing offal (heads, viscera, and feet) was collected on 3 separate days from a commercial processing plant. Each sample was separately ground, supplemented with sucrose (6% initial concentration), inoculated with actively growing lactic acid bacteria (10(6) cfu/g of offal) from a commercial silage culture, and fermented at 37 C. Replicate samples were taken for standard microbiological analysis after 0, 48, and 120 h of fermentation. In fresh offal, heterotrophic plate count, total and fecal coliforms, fecal streptococci, and Aeromonas hydrophila concentrations were 7.4, 5.9, 5.9, 5.4, and 3.9 log10 cfu/g wet weight, respectively. After 48 h of fermentation, the bacterial concentrations were 7.6, 2.2, < 1.3, 5.5, and < 2.3 log10 cfu/g wet weight, respectively. After 120 h of fermentation, the bacterial concentrations were 6.9, < 1.1, < 1.1, < 1.1, and < 1.1 log10 cfu/g wet weight, respectively. Salmonella concentrations in fresh, 48-h fermented, and 120-h fermented offal samples were 3.7, < 1.5, and < 1.5 log10 most-probable-number/100 g wet weight, respectively. Lactic acid fermentation appears to be effective in reducing the number of bacterial pathogens and indicator organisms in poultry processing offal.

Animal Feed↗
PubMed1993

An evaluation of a rinse procedure using sodium bicarbonate and hydrogen peroxide on the recovery of bacteria from broiler carcasses.

A patent entitled "Reduction of Bacteria Count on Poultry Being Processed into Food at a Poultry Processing Plant" (U.S. Patent No. 4,683,618) claimed that a three-step rinse process using sodium bicarbonate and hydrogen peroxide solutions would remove bacteria from the surface of broiler carcasses. In three replicate trials, 40 broilers were obtained postchill from a commercial processing plant. Broilers (n = 20) were treated according to the patent by spraying the inside and outside surfaces of each carcass with a 2% NaHCO3 solution for 5 s and rinsing with water, repeating, spraying with a 3% H2O2 solution for 5 s, and rinsing a final time with water. Controls (n = 20) were treated identically except that in each of the rinse steps tap water was used in place of the test solutions. Whole carcass rinses were conducted and total aerobic plate counts (TPC) and impedance detection times (DT) were determined after 1 h and 7 days at 4 C. The NaHCO3 + H2O2 treatment resulted in no significant difference in TPC at 1 h post-treatment but did result in lower TPC after 7 days and greater DT at both 1 h and 7 days. The procedure was effective in reducing the recovery of bacteria at 7 days post-treatment by .3 log10 but was not effective in removing the bacteria to the extent implied in the patient. Based on previous studies using H2O2, these results are not unexpected, but commercial applicability remains questionable based on actual reduction levels.

Analysis of Variance↗
PubMed1992

Tissue-specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing.

CD46 (membrane cofactor protein) is a human cell surface glycoprotein with cofactor activity for factor I-mediated cleavage of complement components C3b and C4b. The CD46 protein from normal lymphocytes resolves on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two major bands of 66 and 56 kDa. CD46 cDNA encodes four extracellular short consensus repeat domains, a Ser/Thr/Pro (STP)-rich region, a transmembrane region and a cytoplasmic tail. We now show that exquisite control of mRNA splicing is responsible for the heterogeneous expression of CD46 isoforms. Differential splicing of 5 exons generates at least 14 CD46 mRNA variants whose expression is stringently regulated by allelic, tissue-specific and malignancy-related factors, as: (a) leukemic cells and Epstein-Barr virus-transformed B cells preferentially incorporate the first of three STP exons (exon 7) into mRNA, and produce a larger CD46 isoform of 74 kDa, (b) an allelic difference in the proportion of 66- and 56-kDa CD46 isoforms on lymphocytes corresponds to the preferential inclusion or exclusion of the second STP exon (exon 8), (c) the third STP exon (exon 9) is specifically deleted in some placentae, (d) spermatozoa delete both exons 12 and 13, encoding a shorter transmembrane region and a unique cytoplasmic tail and (e) all tissues tested differentially splice exon 13, resulting in two alternative cytoplasmic tails. The distribution of the 14 alternatively spliced RNA transcripts correlated with the presence of protein isoforms of the predicted size, indicating that alternative splicing leads to heterogeneity of CD46 glycoproteins.

Alleles↗
PubMed1992

The specificity of antibodies induced by infection with rhinovirus type 2.

Mouse monoclonal antibodies (MAbs) against three distinct antigenic sites on rhinovirus type 2 have been obtained and the sites identified. We describe how these MAbs were used in a blocking test to detect antibodies in human sera directed against the same three defined sites. Sera from twelve volunteers were studied. All had been exposed to rhinovirus type 2 by intranasal inoculation, four had been uninfected, eight were infected of whom four developed a cold while four did not. Blocking antibodies were high and did not increase in the resistant volunteers, and were lower and increased in the infected volunteers. The antibodies were almost as sensitive as other antibody assays for detecting infection. The responses to all three sites were similar. Correlations between the results of all tests were calculated and the results are summarised. Tests were also devised to measure the Ig subclass of antibodies against the whole virus particle. The A1, G1, and G4 classes showed most frequent rises in response to infection. Correlations between these results and other antibody assays were found and are presented.

Antibodies, Monoclonal↗
PubMed1992

Human astrocytes express membrane cofactor protein (CD46), a regulator of complement activation.

Expression of membrane cofactor protein (CD46) on cultured human astrocytes was demonstrated by indirect immunofluorescence microscopy and flow cytometry following staining with a monoclonal antibody specific for CD46. Western transfer and immunoblotting detected a doublet of Mr 66,000 and 56,000. Analysis of astrocyte mRNA revealed the presence of multiple alternatively spliced transcripts encoding different extracellular regions or cytoplasmic tails of CD46. Astrocytes were also shown to express decay accelerating factor, but not the type 1 complement receptor. Upregulation of astrocyte CD46 occurred following cytomegalovirus infection. These results indicate that astrocytes express proteins involved in regulation of complement activation and protection against autologous complement.

Antigens, CD↗
PubMed1992

Evidence suggesting that insulin-like growth factor-I is necessary for the trophic effects of insulin on cartilage growth in vivo.

The possibility that insulin-stimulated cartilage growth in hypophysectomized rats involves local production of insulin-like growth factor I (IGF-I) was investigated. Osmotic minipumps with attached catheters were used to infuse insulin into the right hindlimb of rats via the common iliac artery for 7 days starting 14 days after pituitary removal. The left, noninfused limb served as an internal control. Doses of insulin ranging from 0.25 to 50 mU/day caused significant increases in the tibial epiphyseal plate width (TEPW) of the infused limbs. The optimal dose of 1.25 mU/day increased the TEPW by 51 microns. Immunohistochemical analysis with an antiserum to human IGF-I showed that the growth response to the optimal dose was accompanied by the accumulation of IGF-I in the chondrocytes in the tibial plate. Infusion of insulin at a dose of 10 mU/day increased the TEPW by 18.6 +/- 3.0 microns. When the same dose of insulin was infused with the antiserum to human IGF-I, the growth response was completely nullified. These results indicate that cartilage cells in hypophysectomized rats are highly sensitive to the direct growth-promoting action of insulin. Furthermore, the growth effect appears to be mediated by or dependent on local production of IGF-I.

Animals↗
PubMed1992

Lactic acid fermentation of broiler processing waste: physical properties and chemical analyses.

Broiler processing waste (offal), consisting of broiler heads, viscera, and feet, was collected from a commercial processing plant, ground, mixed with a fermentable substrate, and inoculated with actively growing organisms from a commercial silage culture. The offal mixture was fermented at 11, 19, and 37 C for up to 48 h and evaluated for pH, odor, and aqueous, solid, and oil fractions produced by centrifugation. Freshly ground offal, fermented offal, and aqueous and solids fractions were analyzed for moisture, fat, and protein content. The oil fraction produced by centrifugation of the fermented offal was analyzed for fatty acid composition. The optimum fermentation conditions, as determined by final pH, were obtained by the addition of 6% sucrose, inoculation with 10(6) cfu of silage culture organisms/kg of offal, and incubation at 37 C. The pH decreased from 6.2 to 3.9 in 24 h. Freshly ground offal and 48-h fermented offal were found to contain 63.2% moisture, 15.9% fat, and 14.9% protein, and 57.3% moisture, 19.1% fat, and 12.9% protein, respectively. The aqueous and solid fractions were 73.3% moisture, 1.1% fat, and 12.1% protein, and 57.7% moisture, 6.8% fat, and 21.8% protein, respectively. Fermentation was effective in decreasing pH, altering the odor and viscosity, and, upon centrifugation, increasing fat recovery and producing fractions that were easily separated.

Animals↗