PubMed Health⌕ Search

Biomedical subjects

T M Ellis

Publications and source records attributed to T M Ellis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Changes in telomerase activity and telomere length during human T lymphocyte senescence.

It has been proposed that telomeres shorten with every cell cycle because the normal mechanism of DNA replication cannot replicate the end sequences of the lagging DNA strand. Telomerase, a ribonucleoprotein enzyme that synthesizes telomeric DNA repeats at the DNA 3' ends of eukaryotic chromosomes, can compensate for such shortening, by extending the template of the lagging strand. Telomerase activity has been identified in human germline cells and in neoplastic immortal somatic cells, but not in most normal somatic cells, which senesce after a certain number of cell divisions. We and others have found that telomerase activity is present in normal human lymphocytes and is upregulated when the cells are activated. But, unlike the immortal cell lines, presence of telomerase activity is not sufficient to make T cells immortal and telomeres from these cells shorten continuously during in vitro culture. After senescence, telomerase activity, as detected by the TRAP technique, was downregulated. A cytotoxic T lymphocyte (CTL) cell line that was established in the laboratory has very short terminal restriction fragments (TRFs). Telomerase activity in this cell line is induced during activation and this activity is tightly correlated with cell proliferation. The level of telomerase activity in activated peripheral blood T cells, the CTL cell line, and two leukemia cell lines does not correlate with the average TRF length, suggesting that other factors besides telomerase activity are involved in the regulation of telomere length.

Adult↗
PubMed1997

Dermatophilus congolensis: strain differences in expression of phospholipase activities.

Interactions between Dermatophilus congolensis strains and with other bacteria of known haemolytic activities were used to elucidate the complex nature of haemolytic activities present in various D. congolensis strains. This was further analysed by measuring their specific phospholipase activities against defined substrates by thin layer chromatography. D. congolensis strains demonstrated haemolytic interactions (synergistic or antagonistic) with other D. congolensis strains and also other species of bacteria. Most isolates expressed lyso-phospholipase-D activity, while various strains also expressed sphingomyelinase-D activity, phospholipase-A versus phosphatidylcholines and/or cephalins, phospholipase-D versus phosphatidylcholines or all these activities, under the culture conditions used.

Actinomycetales↗
PubMed1997

Cellular immune reactivities in women with silicone breast implants: a preliminary investigation.

BACKGROUND: Surgical implantation of silicone breast prostheses has been conducted and considered safe for over 30 years. Some implant recipients, however, complain of a group of symptoms similar to those observed in connective tissue disorders, rheumatoid arthritis, systemic lupus erythematosus, or polymyositis. To date, immunologic sequelae have not been confirmed and remain controversial. OBJECTIVE: To examine an autoimmune-like basis for the "silicone associated disease" reported by some women with silicone breast prostheses. METHODS: Proliferative responses of peripheral blood mononuclear cells against a panel of control and connective tissue proteins and to compounds common to silicone prostheses were measured in 26 women who received silicone breast implants (with implants in place an average of 166.4 [standard deviation (SD) 58.3] months), and 23 age-matched and sex-matched healthy controls. RESULTS: The frequency and intensity of cellular immune responses against collagen I, collagen III, fibrinogen, and fibronectin were significantly increased in silicone breast implant recipients versus controls. In implant subjects, the highest frequency of immune reactivity was directed against collagen I (11/26, 42%) with collagen III being the most immunostimulatory self-antigen with a mean stimulation index (SI) of 8.2 [95% confidence interval (95% CI) 3.2]. In addition, 10/26 (39%) of the implant recipients responded to more than one of the connective tissue antigens versus 0/23 (0%, P = .0007) healthy controls. Immunologic reactivities to other antigens, including silicone-based compounds, were remarkably similar. CONCLUSIONS: The identification of self-reactivity towards these connective tissue antigens may provide important information for attempts at associating silicone breast implants with disease.

Adult↗
PubMed1997

Infants diets and insulin-dependent diabetes: evaluating the "cows' milk hypothesis" and a role for anti-bovine serum albumin immunity.

Insulin-Dependent Diabetes (IDD) results from an autoimmune destruction of the insulin secreting pancreatic beta cells. The immunological mechanisms underlying the development of IDD as well as the role of environmental agents (e.g., diet, viruses, stress) in the pathogenesis of the disease are the subject of considerable research efforts. Significant attention has recently been directed to a hypothesis that consumption of cows' milk in infancy may trigger the autoimmune process underlying IDD. Early evidence supporting this "cows' milk hypothesis" included case-control studies surveying infant nutrition practices (i.e., breast feeding versus consumption of infant formula) and the subsequent development of IDD. However, intense media interest surrounding a report indicating anti-bovine serum albumin (BSA) immunity as the cause of IDD has lead to heightened public awareness of the issue, and, together with the epidemiological data, prompted The American Academy of Pediatrics to modify its guidelines for infant feeding practices. However, less public and scientific attention has been given toward the observations that many of these case-control studies were retrospective in design and subject to recall bias, narrow in scope in terms of collecting dietary information, and that similar results have not been duplicated in other more recent (and better designed) investigations. Furthermore, the immunological report implicating anti-BSA immunity with the disease has become controversial due to difficulties in conforming the findings, and experiments in animal models closely resembling human IDD have not uniformly supported a role for anti-BSA immunity in the pathogenesis of IDD. Given the significant morbidity and mortality associated with IDD, an improved understanding of the cause of this disorder as well as identifying possible methods for its prevention are essential. However, without additional supporting information, modification of the cows' milk/BSA composition of diets in order to avoid the disease may be premature. Further studies are needed to clearly establish a role for diet in the pathogenesis of IDD.

Animals↗
PubMed1996

Differential sensitivity of resting and IL-2 activated NK cells to R-verapamil.

Natural killer (NK) cells are the first lymphoid population to reconstitute the peripheral blood compartment of immunologically compromised bone marrow transplant (BMT) recipients. Recent data suggest that, among patients transplanted for leukemia, NK cells can prevent or delay disease relapse by mediating a cytotoxic graft vs leukemia (GvL) response. Although the major mechanism by which NK cells mediate target cell lysis involves degranulation and release of cytolytic effector molecules (granzymes, proteoglycans, perforin), accumulating evidence suggests that NK cells possess additional pathways to mediate target cell killing. In fact, it is well recognized that recombinant cytokines such as IL-2 enhance the in vitro cytolytic activity of NK cells. In this study, we observed that the lytic activity mediated by resting and IL-2 activated NK cells against the same target cell appears to occur via two distinct pathways, as distinguished by their differential response to R-verapamil. Specifically, we observed that 25 microM R-verapamil inhibited the lytic activity of resting NK cells against K562 targets by approximately 50%. However, the lytic activity of IL-2 activated NK cells was unaffected by this concentration of R-verapamil. Additional studies suggested that the inhibitory effect of R-verapamil on NK cytotoxic activity was associated with its ability to prevent degranulation of cytotoxic granules. Specifically, R-verapamil inhibited BLT esterase release from resting but not IL-2 activated NK cells. These data suggest that IL-2 activated NK cells can promote target cell lysis by a pathway (possibly degranulation independent) distinct from that used by resting NK cells. We speculate that the target of R-verapamil on resting NK cells is P-glycoprotein (Pgp), an ABC transporter that we recently reported was expressed on NK cells and whose functional activity is known to be inhibited by R-verapamil.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

CD2 regulates T cell-dependent induction of monocyte IL-1 beta mRNA during anti-CD3 mitogenesis.

The induction of monocyte IL-1 mRNA during T cell activation requires that monocytes receive contact-dependent signals from activated T cells. Furthermore, the ability of T cells to induce IL-1 beta mRNA is not constitutive but rather is rapidly acquired (< or = 30 min) following activation via mechanisms that do not require protein synthesis. The goal of these studies is to identify the T cell signal(s) that mediates the cell contact-dependent induction of monocyte IL-1 beta mRNA. The induction of IL-1 beta mRNA during anti-CD3 mitogenesis was significantly inhibited by anti-CD2 mAb, whereas mAb against CD11a, CD18, CD69, or CD5 molecules had no effect. The inhibition of IL-1 beta mRNA induction by anti-CD2 mAb was restricted to only those mAb that block CD2/CD58(LFA-3) interactions. Furthermore, anti-CD2 blocked the induction of monocyte IL-1 beta mRNA by T cells that were preactivated using either immobilized anti-CD3 or anti-T11(2) plus anti-T11(3) mAb, thereby indicating that the inhibition of IL-1 beta mRNA was not due to negative signaling effects exerted on the T cell by anti-CD2. Finally, although anti-CD69 mAb had no effect on IL-1 beta mRNA induction, it inhibited the generation of soluble IL-1 beta. The combination of anti-CD69 and anti-CD2 mAb exhibited greater inhibition of secreted IL-1 beta than either antibody alone. These results indicate that CD2 is required for T cell induction of IL-1 beta mRNA through interaction with LFA-3 on the monocyte and that the generation of soluble IL-1 beta is regulated by CD69.

Antibodies, Monoclonal↗
PubMed1996

A reversible defect in alpha-beta T cell receptor assembly.

A human leukemia cell line, SUP-T13, can gain and lose TCR/CD3 expression at rates incompatible with spontaneous mutation. In this study, we determined (i) the generality of this phenomenon among other T cell lines, (ii) the specificity of this phenomenon to the TCR/CD3 complex, and (iii) the molecular mechanism of TCR/CD3 loss in the SUP-T13 cell line at a biochemical level. We show that two other T cell lines can undergo gain and loss of TCR/CD3 expression at similar rates. However, class I MHC molecules do not switch expression on and off, demonstrating that such switching is not an artifact of the analysis. To determine the mechanism for loss of surface TCR/CD3 expression, pulse-chase labeling and immunoprecipitation were performed on SUP-T13 TCR/CD3 negative cells. These analyses revealed that TCR alpha proteins are produced, but do not covalently associate with TCR beta-CD3 proteins in the negative cells. Thus, these variants represent a novel level of posttranslational regulation of TCR/CD3 expression, namely, the disulfide linkage of alpha and beta TCR chains.

Glycosylation↗
PubMed1996

Nitric oxide inhalation: effects on the ovine neonatal pulmonary and systemic circulations.

Others have shown that inhaled nitric oxide causes reversal of pulmonary hypertension in anaesthetized perinatal sheep. The present study examined haemodynamic responses to inhaled NO in the normal and constricted pulmonary circulation of unanaesthetized newborn lambs. Three experiments were conducted on each of 7 lambs. First, to determine a minimum concentration of NO which could reverse acute pulmonary hypertension caused by infusion of the thromboxame mimic U46619, the haemodynamic effects of 5 different doses of inhaled NO were examined. Second, the effects of inhaling 80 ppm NO during hypoxic pulmonary vasoconstriction were examined. Finally, to determine if tachyphalaxis occurs during NO inhalation, lambs were exposed to 80 ppm NO for 3 h during which time pulmonary arterial pressure was doubled by infusion of U46619. Breathing NO (80 ppm) caused a slight but significant decrease in pulmonary vascular resistance (PVR) in lambs with normal pulmonary arterial pressure (PAP). Nitric oxide, inhaled at concentrations between 10 and 80 ppm for 6 min (F1O2 = 0.60), caused decreases in PVR when PAP was elevated with U46619. Nitric oxide acted selectively on the pulmonary circulation, i.e. no changes occurred in systemic arterial pressure or any other measured variable. Breathing 80 ppm NO for 6 min reversed hypoxic pulmonary vasoconstriction. In the chronic exposure study, inhaling 80 ppm NO for 3 h completely reversed U46619-induced pulmonary hypertension. Although arterial methaemoglobin increased during the 3-h exposure to 80 ppm NO, there was no indication that this concentration of NO impairs oxygen loading. These data demonstrate that NO, at concentrations as low as 10 ppm, is a potent, rapid-action, and selective pulmonary vasodilator in unanaesthetized newborn lambs with elevated pulmonary tone. Furthermore, these data support the use of inhaled NO for treatment of infants with pulmonary hypertension.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Use of enzyme-linked immunoassays for antibody to types C and D botulinum toxins for investigations of botulism in cattle.

The development of specific enzyme-linked immunosorbent assays (ELISA) for antibody to types C and D Clostridium botulinum toxins for investigation of botulism in cattle is described. Partially purified type C and D toxins were used as antigens to develop these ELISAs. Specificity of the ELISAs was evaluated on sera from 333 adult beef and dairy cattle from areas with no history or evidence of botulism in animals or water birds. The test was also evaluated on sera from 41 herds that included herds vaccinated against botulism, confirmed botulism cases and herds from areas where the disease is considered endemic. The ELISAs detected the presence of antibody to botulinum toxins in samples from vaccinated cattle and both convalescent and clinically normal animals from unvaccinated herds with outbreaks of botulism. Antibody was also found in unvaccinated animals from herds in which there had been no diagnosed botulism cases in areas where botulism was considered endemic. Sera from some unvaccinated cattle with high ELISA reactivity was shown to be protective for mice in botulinum toxin neutralisation tests. The use of these tests in investigations of botulism in cattle is discussed.

Animals↗
PubMed1996

Utility of flow cytometric detection of CD69 expression as a rapid method for determining poly- and oligoclonal lymphocyte activation.

CD69 is a lymphoid activation antigen whose rapid expression (< or = 2 h postactivation) makes it amenable for the early detection of T-cell activation and for subset activation analyses. In the present study we evaluated the utility of flow cytometric detection of CD69 expression by T cells activated with polyclonal stimuli (anti-CD3 and staphylococcal enterotoxin B [SEB]) and oligoclonal stimuli (tetanus toxoid and allogeneic cells) using flow cytometry. Following activation of T cells with anti-CD3 or SEB, CD69 is detectable at < or = 4 h following activation, with anti-CD3 peaks at 18 to 48 h. Dose titration experiments indicated that CD69 expression largely paralleled that in [3H]thymidine incorporation assays, although the former offered a more sensitive measure of T-cell activation at limiting doses of activator than [3H]thymidine incorporation when cells were activated with either anti-CD3 or SEB. However, activation of T cells with either tetanus toxoid or allogeneic stimulator cells failed to induce detectable CD69 expression at up to 7 days of culture. Subset analyses of anti-CD3- and SEB-activated T cells indicated that populations other than T cells can express CD69 following stimulation with T-cell-specific stimuli, indicating that CD69 can be induced indirectly in non-T cells present in the population. These findings indicate that CD69 is a useful marker for quantifying T-cell and T-cell subset activation in mixed populations but that its utility might be restricted to potent stimuli that are characterized by their ability to activate large numbers of cells with rapid kinetics.

Adult↗
PubMed1996

Immunological and metabolic effects of prophylactic insulin therapy in the NOD-scid/scid adoptive transfer model of IDDM.

Prophylactic insulin therapy prevents IDDM in spontaneous animal models of the disease and has shown promise in preventing the disease in humans. Although large clinical trials have been formed to use this therapy, a comparative analysis of the efficiency of different pharmaceutical forms and doses of insulin in preventing IDDM has not been performed, and the mechanism underlying the observed prevention of disease is unknown. In the NOD-scid/scid adoptive transfer model of IDDM (10(7) new-onset NOD splenocytes injected intravenously into 6- to 8-week NOD/scid-scid recipients; insulitis develops at 6-9 days post-transfer and 100% IDDM by 32 days post-transfer), life-table (log-rank) analyses revealed that IDDM can be delayed (compared with insulin-free diluent, once daily, n = 8) with equivalent efficiency by prophylactic administration (-9-50 days post-transfer) of high (metabolism-altering) doses of short-acting (0.5 U, once daily, regular, n = 13) or long-acting (0.5 U, once daily, ultralente, n = 9) insulin as well as non-metabolism-altering low-dose insulin (0.02 U, once daily, regular, n = 8). Furthermore, IDDM was delayed with somatostatin (0.2 microgram, twice daily, n = 11), an agent that suppresses endogenous insulin production. No significant difference was seen between the preventative effects of these agents. In an assessment of when therapies can be initiated and still maintain clinical efficiency, only prophylactic somatostatin therapy delayed IDDM (n = 10, P = 0.02) when initiated at 14 days post-transfer, whereas the short-acting insulin regimen did not retard the onset of IDDM (n = 8, P = 0.25) compared with diluent-treated controls. The 24-h urinary C-peptide levels were significantly reduced with short-acting (-56%, P = 0.01) and long-acting (-67%, P = 0.02) insulin products and somatostatin (-59%, P = 0.02) compared with diluent-treated controls. These results indicate that both immunological and metabolic (i.e., beta-cell rest) factors may contribute to the beneficial effects of prophylactic insulin therapy.

Animals↗