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Biomedical subjects

S M Russell

Publications and source records attributed to S M Russell.

At least 19 recordsLinked to original sources
PubMed1996

Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation.

One of the earliest events induced by interleukin 2 (IL-2) is tyrosine phosphorylation of cellular proteins, including the IL-2 receptor beta chain (IL-2Rbeta). Simultaneous mutation of three tyrosines (Y338, Y392, and Y510) in the IL-2Rbeta cytoplasmic domain abrogated IL-2-induced proliferation, whereas mutation of only Y338 or of Y392 and Y510 inhibited proliferation only partially. While Y392 and Y510 were critical for IL-2-induced activation of signal transducers and activators of transcription (STAT proteins), Y338 was required for Shc-IL-2Rbeta association and for IL-2-induced tyrosine phosphorylation of Shc. Thus, activation of both Jak-STAT and Shc-coupled signaling pathways requires specific IL-2Rbeta tyrosines that together act in concert to mediate maximal proliferation. In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1996

A dissection of the chapter "Tools for Research" in Peter Singer's Animal Liberation.

The book Animal Liberation, by philosopher Peter Singer, is frequently referred to as the bible of the animal liberation/rights movement(ALARM). Thus, Singer is regarded as a major moral standard-bearer of the ALARM. Some have suggested that his book provides "intellectual rigor" to the moral arguments for animals' equality with humans, which had previously been based largely on emotionalism and sentimentality. We have analyzed the contents of the chapter "Tools for Research" which criticizes the use of animals in biomedical research as well as for drug and product-safety testing. In order to discredit these practices, Singer "documents" his arguments with 138 "notes", some of which are to the same reference and others of which contain multiple references. Of the 132 difference references, we attempted to verify the accuracy of 49 of them. Of these, 16 (33%) were inaccurate or we could not find. In addition, Singer mischaracterizes the cited studies in various ways. He quotes selectively and out of context from numerous research projects. He never mentions the objectives of these projects, except occasionally when, in our opinion, he distorts or trivializes them. Singer also cites supposedly damning "evidence" published by other antivivisectionists, even though this "evidence" has been refuted in the literature. Singer supposedly embraces utilitarianism, a philosophy which holds that the harm done by a practice should be balanced against the gain realized from it. However, he makes virtually no attempt to consider objectively the benefits that have been realized from animal-based medical research and he greatly exaggerates the costs. To him, animal research is "all pain and no gain." We believe that Singer's moral arguments for animal equality are not convincing. The lack of objectivity and the reliance upon distortion and selective quotation that characterize Singer's "scholarship" are surprising when one considers that he presents himself as an ethicist and moralist.

Animal Rights↗
PubMed1996

The effect of temperature mishandling at various times during storage on detection of temperature abuse of fresh broiler chicken carcasses.

Experiments were conducted to determine the effect that temperature mishandling at various times during storage has on detection of temperature abuse of fresh broiler chicken carcasses using populations of mesophilic and coliform bacteria as indicators of abuse. Forty-five broiler carcasses were used in each of three independent trials. Five carcasses were analyzed at day of collection (Treatment 0 control). Five carcasses, on each day of the next 7 d (Treatments 1 to 7) were temperature-abused for 12 h at 25 C, stored at 3 C until Day 9, and then sampled. The five remaining carcasses were stored at 3 C and sampled on Day 9 (Treatment 8 control). Carcasses were sampled using a whole carcass rinse procedure and assayed for aerobic plate counts (APC), total coliform counts (TCC), impedance detection times (DT), and impedance coliform detection times (DTCM). Although significant differences were noted using all four microbiological methods, temperature abuse at different times during storage had no consistent effect on populations of mesophilic or coliform bacteria; therefore, temperature abuse determinations may be conducted without regard to the day on which the carcasses were subjected to elevated temperatures.

Animals↗
PubMed1995

Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.

Males with X-linked severe combined immunodeficiency (XSCID) have defects in the common cytokine receptor gamma chain (gamma c) gene that encodes a shared, essential component of the receptors of interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15. The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c, so it was hypothesized that defects in Jak3 might cause an XSCID-like phenotype. A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis. An Epstein-Barr virus (EBV)-transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA. Sequencing revealed a different mutation on each allele: a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain. The lack of Jak3 expression correlated with impaired B cell signaling, as demonstrated by the inability of IL-4 to activate Stat6 in the EBV-transformed cell line from the patient. These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling.

Amino Acid Sequence↗
PubMed1995

Expression of interleukin-2 receptor gamma on human monocytes: characterization of lineage specific post-translational modifications.

Functional interleukin-2 receptors (IL-2R) on lymphocytes contain both IL-2R beta and gamma chains. Whereas constitutive expression of IL-2R beta has been found on monocytes, the expression of IL-2R gamma on these phagocytes has not been examined. We performed reverse-transcription-polymerase chain reaction with Southern blot analysis on RNA derived from purified human monocytes and discovered that they constitutively produce IL-2R gamma mRNA. Western immunoblotting revealed 58- and 64-kDa forms of IL-2R gamma on YT-1 and human monocytes, whereas 58-, 64-, and 69-kDa bands were detected using peripheral blood mononuclear cells and non-adherent lymphocytes. These different forms resulted from variable N-linked glycosylation since culture of the cells in tunicamycin resulted in detection of a single 39-kDa band which corresponds to the molecular weight predicted from the deduced amino acid sequence. By co-immunoprecipitation, the IL-2R beta subunit associates with only the 64-kDa IL-2R gamma protein band in monocytes.

Blotting, Southern↗
PubMed1995

Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain.

The common gamma chain (gamma c) of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors is defective in humans with XSCID. Mice lacking gamma c expression had hypoplastic thymuses; the thymocytes responded to gamma c-independent mitogens, but not gamma c-dependent stimuli. Splenic T cells were diminished at 3 weeks of age, but CD4+ T cells markedly increased by 4 weeks. B cells were greatly diminished in contrast with the situation in XSCID. NK cells, gamma delta intestinal intraepithelial lymphocytes, dendritic epidermal T cells, peripheral lymph nodes, and gut-associated lymphoid tissue were absent. These findings underscore the importance of gamma c in lymphoid development. Moreover, differences in humans and mice lacking gamma c expression indicate species-specific differences in the roles of gamma c-dependent cytokines or in the existence of redundant pathways. These mice provide an important model for studying the pathophysiology provide an important model for studying the pathophysiology of and gene therapy for human XSCID.

Animals↗
PubMed1995

Retroviral vector for gene therapy of X-linked severe combined immunodeficiency syndrome.

X-linked severe combined immunodeficiency syndrome (X-SCID) is a genetic disorder characterized by profound impairment of cell-mediated and humoral immunity. Affected children die of recurrent infections within 2 years of birth unless rescued by allogeneic transplantation from a suitable donor. Recently, the genetic defect responsible for X-linked SCID has been identified as a mutation in the gamma chain of the IL-2 receptor, a protein also shared by the IL-4 and IL-7 receptors and therefore now denoted the common gamma chain (gamma c). We report here the development of a high-titer amphotropic retroviral vector for transfer of gamma c. This vector was used to transfer a copy of the gamma c cDNA to murine 3T3 fibroblasts, CD34-enriched hematopoietic progenitor cells obtained from bone marrow and umbilical cord blood of normal donors, and to transplanted murine bone marrow progenitors. Murine 3T3 cells transduced by the retroviral vector were analyzed by Southern blot hybridization and Western transfer. Southern analysis confirmed the integration of unrearranged proviral DNA, and Western blot analysis demonstrated the expression of gamma c protein. CD34-enriched cells were infected with viral vectors bearing gamma c and grown in methylcellulose media. Individual colonies and pools of cells were analyzed 2 weeks later by polymerase chain reaction assay, which confirmed the proviral marking. The vector was also used to transfer a copy of the gamma c cDNA to murine bone marrow cells in a transplantation model. Infected marrow was transplanted into syngeneic Balb/c mice.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

Spoilage bacteria of fresh broiler chicken carcasses.

Studies were conducted to identify the bacteria responsible for spoilage of fresh broiler chicken carcasses and to characterize the off-odors these bacteria produce. Broiler carcasses were collected from processing plants in the northeast Georgia area, the southeastern U.S., Arkansas, California, and North Carolina. The carcasses were allowed to spoil under controlled conditions at 3 C and spoilage bacteria were isolated. Each spoilage bacterium was separately inoculated into a sterile chicken skin medium, incubated at 25 C for 48 h, and subjectively evaluated for odor. The bacteria isolated from spoiled carcasses that consistently produced off-odors in the chicken skin medium, regardless of the geographical location from which the chickens were obtained, were Shewanella putrefaciens A, B, and D, Pseudomonas fluorescens A, B, and D, and Pseudomonas fragi. These bacteria produced off-odors that resembled "sulfur", "dishrag", "ammonia", "wet dog", "skunk", "dirty socks", "rancid fish", "unspecified bad odor", or a sweet smell resembling "canned corn". Odors produced by the spoilage bacteria were varied; however, odors most associated with spoiled poultry, such as "dishraggy" odors, were produced by the bacteria that were most consistently isolated, such as S. putrefaciens and the pseudomonads.

Acinetobacter↗
PubMed1995

The effect of refrigerated and frozen storage on populations of mesophilic and coliform bacteria on fresh broiler chicken carcasses.

Experiments were conducted to determine whether lots of broiler chicken carcasses analyzed at Day 0 or subjected to various refrigeration or freezing temperatures could be microbiologically differentiated using impedance microbiological methods. Sixty ready-to-cook broiler chicken carcasses were collected from a processing facility and used in each of three replicate trials. For each trial, 10 carcasses each were: sampled immediately (Day 0 control), sampled after holding at 3 C for 13 d (Refrigerated control), sampled after holding at 0 C for 12 d and tempering at 3 C for 24 h (Refrigerated 0), sampled after holding at -3.9 C for 12 d and tempering at 3 C for 24 h (Frozen -3.9), sampled after holding at -7.8 C for 12 d and tempering at 3 C for 24 h (Frozen -7.8), and sampled after holding at -27.0 C for 12 d and tempering at 3 C for 24 h (Frozen -27). Carcasses were sampled using a whole carcass rinse procedure. Mesophilic impedance detection times (MDT) and coliform impedance detection times (CDT) at 42 C were conducted in duplicate on each carcass rinse. Lots of carcasses held at 0 C or below had significantly fewer mesophiles than those held at 3 C. The MDT would be suitable for distinguishing carcasses held at 0 C or below from those held at 3 C. Using CDT, lots of carcasses frozen at -7.8 or -27.0 C could be distinguished from lots analyzed at Day 0 or held at 0 or 3 C. Using CDT, lots of carcasses frozen at -3.9 could not be separated from those held at 3 C, but could be distinguished from those held at 0 C. Monitoring coliforms using impedance would be useful for identifying lots of carcasses subjected to temperatures of -7.8 C or below but would not be suitable for determining freezing temperature.

Animals↗
PubMed1994

Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID.

Interleukin-2 (IL-2) signaling requires the dimerization of the IL-2 receptor beta.(IL-2R beta) and common gamma (gamma c) chains. Mutations of gamma c can result in X-linked severe combined immunodeficiency (XSCID). IL-2, IL-4, IL-7 (whose receptors are known to contain gamma c), and IL-9 (whose receptor is shown here to contain gamma c) induced the tyrosine phosphorylation and activation of the Janus family tyrosine kinases Jak1 and Jak3. Jak1 and Jak3 associated with IL-2R beta and gamma c, respectively; IL-2 induced Jak3-IL-2R beta and increased Jak3-gamma c associations. Truncations of gamma c, and a gamma c, point mutation causing moderate X-linked combined immunodeficiency (XCID), decreased gamma c-Jak3 association. Thus, gamma c mutations in at least some XSCID and XCID patients prevent normal Jak3 activation, suggesting that mutations of Jak3 may result in an XSCID-like phenotype.

Animals↗
PubMed1994

The gamma subunit of the interleukin-2 receptor is expressed in human monocytes and modulated by interleukin-2, interferon gamma, and transforming growth factor beta 1.

The interleukin-2 receptor gamma (IL-2R gamma) chain is a newly recognized component of the IL-2R of lymphoid cells that is required for their response to IL-2. We investigated the expression of IL-2R gamma protein in human monocytes by Western blot analysis using an antiserum specific for IL-2R gamma. We found that IL-2R gamma subunit is constitutively expressed in human monocytes and upregulated by the monocyte-activating factors IL-2 and interferon gamma (IFN gamma). Furthermore, we show that transforming growth factor beta 1 (TGF beta 1) downmodulates, in a dose-dependent manner, basal and IL-2-induced, but not IFN gamma-induced, IL-2R gamma chain expression, and this effect may be responsible for TGF beta 1 suppressive activity on IL-2-activated monocytes. Overall, these results show that the expression of the IL-2R gamma subunit in human monocytes is tightly regulated by the cytokine network, suggesting a critical role played by this protein on monocyte activation.

Dose-Response Relationship, Drug↗
PubMed1994

Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling.

The interaction of interleukin-2 (IL-2) and IL-2 receptors critically regulates the T-cell immune response following antigen activation. IL-2 can signal through high or intermediate affinity receptors which contain IL-2R alpha (refs 3, 4) +beta (refs 5-8) +gamma (ref. 9) or beta+gamma chains, respectively. IL-2R gamma is a common gamma chain, gamma c, also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency. Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the beta- and gamma c-chain cytoplasmic domains. Anti-IL-2R alpha monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracellular domains of IL-2R beta and gamma c are replaced by that of IL-2R alpha. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2R alpha and that the beta-transmembrane domain is not required for receptor chain interactions. Finally, we provide a method for mapping residues in the gamma c cytoplasmic domain even in cells that constitutively express gamma c.

Animals↗
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↗