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Biomedical subjects

A T Nguyen

Publications and source records attributed to A T Nguyen.

At least 55 records · Page 3Linked to original sources
PubMed1993

Soluble CD23 as an effector of immune dysregulation in chronic uremia and dialysis.

Patients with chronic renal failure often present an immunodeficiency state paradoxically exacerbated by hemodialysis and associated with signs of T cell activation. The presence of circulating monokines suggests that monocytes are also activated. Whether or not this includes B cells is controversial, despite frequently abnormal antibody responses. We thus investigated whether the soluble low-affinity receptor for IgE (Fc epsilon RII/CD23), recently identified as a marker of B cell and monocyte activation and possibly involved in T cell activation, was modulated by chronic renal failure and hemodialysis. Relative to values in healthy individuals (N = 31), plasma concentrations of soluble CD23 were significantly elevated in non-dialyzed chronically uremic patients (N = 44), more elevated in patients on peritoneal dialysis (N = 24), and most elevated in those on regular hemodialysis (N = 132), stabilizing after about six months. Soluble CD23 levels were unmodified by the first dialysis session but rose markedly during regular dialysis with cellulose or polysulfone membranes, but not with polyacrilonitrile AN-69 membranes. Soluble CD23 levels correlated with levels of IgG, and those of tumor necrosis factor alpha and interleukin-6, suggesting that increased sCD23 levels reflect activation of B cells and monocytes, respectively. These findings reinforce the view of soluble CD23 as a multi-functional receptor/cytokine, and provide evidence that it might contribute to the immune dysregulation associated with chronic renal failure and exacerbated by hemodialysis.

Adolescent↗
PubMed1993

Quality of care and outcomes of chronic mentally ill patients in hospitals and nursing homes.

OBJECTIVE: Quality of care in three types of facilities in which chronic mentally ill patients reside was examined to determine how it was related to patient functioning and to determine how patients' dependency on others for self-care moderated relationships between quality of care and patient functioning. METHODS: Discriminant function analyses and multiple regression analyses were used to examine 12-month follow-up data from a Department of Veterans Affairs (VA) study of 294 chronic mentally ill patients in 52 community nursing homes, nine VA nursing home care units, and 43 VA hospital psychiatric units. RESULTS: The three types of facilities were best differentiated by staff and resident characteristics and facility policies. Residents of community nursing homes were more impaired, and staff were less well trained, than in the VA facilities. The community nursing homes had less restrictive policies. Patients who lived in facilities that gave them more control over their daily lives and that had larger proportions of high-functioning patients reported more life satisfaction and vigor. Patients in facilities with more social and recreational activities reported less life satisfaction. The extent to which facility features were beneficial or harmful was related to patients' self-care dependency. Supportive physical features and living-assistance services tended to aid impaired residents, whereas more experienced staff and policies that promoted control by residents tended to aid independent residents. CONCLUSIONS: Program managers may need to tailor facility environments to patients' level of functioning to maximize beneficial effects.

Activities of Daily Living↗
PubMed1992

Microtiter plate assay for phagocyte-derived taurine-chloramines.

Despite their potential importance, the role of phagocyte-derived chloramines ("long-lived oxidants") has not yet been investigated in inflammatory or infectious diseases. We have developed a sensitive spectrophotometric microtiter plate assay for chloramines based on their capacity to oxidize potassium iodide (KI). Consistent levels of endogenous chloramines were detected in normal human polymorphonuclear neutrophil (PMN) supernatants after stimulation by phorbol myristate acetate (PMA) or opsonized zymosan. Exogenous taurine strongly enhanced chloramine secretion and was used to quantify the chlorinating potential of PMN. Taurine-chloramines were also detectable in monocyte supernatants, although in smaller amounts. The specificity of the KI assay was assessed both in terms of effect of compounds inhibiting (KBr) or interacting with (sodium azide and catalase) chloramine formation and by showing that PMN from patients with chronic granulomatous disease, due to a hereditary lack of oxidative response capacity, were unable to produce chloramines. Taurine-chloramine levels secreted by PMA (but not zymosan)-stimulated PMN were closely related to the cellular luminol-amplified chemiluminescence (CL) responses although the CL assay failed to detect chloramines in PMN supernatants. We consider that this KI assay should be of use in studying the role of long-lived phagocyte-derived oxidants in clinical medicine.

Chloramines↗
PubMed1992

Pholasin: a new chemiluminescent probe for the detection of chloramines derived from human phagocytes.

We have previously reported that normal human polymorphonuclear neutrophils (PMN) release taurine-chloramine, a long-lived oxidant, in response to stimulation by phorbol myristate acetate (PMA) or opsonized zymosan in the presence of exogenous taurine. We now describe a new, simple, and highly sensitive method for the detection of chloramines, including taurine-chloramine, using the chemiluminescent probe Pholasin, the luciferin of the mollusc Pholas dactylus. Taurine-chloramine (N-chlorotaurine) detection was assessed with both a colorimetric method (based on the oxidation of potassium iodide) and with the Pholasin-dependent chemiluminescence (CL) method. The taurine-chloramine concentration in PMN supernatants determined using the potassium iodide (KI) method correlated closely with Pholasin-dependent CL. This CL was also assessed in nonoxidative conditions. No taurine-chloramine was detected in supernatants of lymphocytes and PMN from patients with an oxidative burst defect (chronic granulomatous disease, CGD) with the KI method, but Pholasin-dependent CL was consistently observed. The use of methionine, a specific chloramine scavenger in our incubation conditions, allowed us to define a methionine-inhibitable fraction of Pholasin-dependent CL (i.e., chloramine-induced CL).

Child↗
PubMed1992

Induction of cytokines by dialysis membranes in normal whole blood: a new in vitro assay for evaluating membrane biocompatibility.

We investigated the capacity of cellulose cuprophane (CUP) and synthetic polyacrylonitrile dialysis membranes to induce the production of interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha using an in vitro model in which normal whole blood is incubated directly with calibrated membrane fragments. We found that only CUP membranes significantly increased plasma levels of IL-1, IL-6, and tumor necrosis factor alpha. The participation of lipopolysaccharide was excluded, since its addition to whole blood incubated with CUP led to a synergistic enhancement of IL-1 production, while the addition of polymyxin B had no significant effect. Transfer experiments showed that CUP-pretreated plasma was able to induce cytokine production by autologous monocytes. Inactivation of complement components prior to pretreatment abolished this effect. The participation of complement activation was further revealed by a correlation between cytokine and C5a plasma levels. Lastly, incubation of isolated monocytes with CUP but not with polyacrylonitrile also induced cytokine production, although to a lesser degree. In conclusion, our simple in vitro model can be used to evaluate the biocompatibility of dialysis membranes directly by using whole blood with greater relevance to the in vivo situation than models based on isolated blood components.

Acrylic Resins↗
PubMed1991

A marked drop in the incidence of the null allele of the B gene of the fourth component of complement (C4B*Q0) in elderly subjects: C4B*Q0 as a probable negative selection factor for survival.

The incidence of allotypes of the genes of the fourth component (C4) and factor B of the complement system was compared in 252 persons under 45 years of age ("young" group) with 482 people between 61 and 90 years of age ("old" group). One hundred people older than 90 years of age (nonagenarians) were also investigated. A striking difference was found between the "young" and "old" groups in the incidence (16.1% and 5.4%, respectively) of a silent gene of the C4B allele (C4B*Q0). This difference was even more marked among "young" and "old" men (17.6% vs 3.4%). The incidence of the C4B*Q0 allele in women dropped to the level of the men only in the nonagenarian group. The most probable explanation for this finding is that people carrying the C4B*Q0 allele die from as yet unidentified disease(s) in their middle-age. Therefore, male (and to a lesser extent female) carriers of this allele may have a considerably shorter life expectancy than individuals without a silent gene in the C4B locus.

Adult↗
PubMed1991

Elevated circulating levels of interleukin-6 in patients with chronic renal failure.

In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNF alpha) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNF alpha, including the induction of the acute phase response of the inflammatory process. Forty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested for plasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P less than 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗
PubMed1991

Influence of first and long-term dialysis on uraemia-associated increased basal production of interleukin-1 and tumour necrosis factor alpha by circulating monocytes.

In a previous study we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term haemodialysis patients and of tumour necrosis factor alpha (TNF alpha) in both long-term haemodialysis and not-yet-dialysed uraemic patients. The present report investigates the spontaneous capacity of monocytes to produce and secrete these two cytokines in 35 long-term haemodialysis patients and 36 uraemic patients undergoing their first dialysis session. Predialytic cell-associated IL-1 concentrations in freshly isolated monocytes were significantly increased both in long-term haemodialysis and first-dialysis uraemic patients compared to normal individuals. In both groups in comparison to normal individuals, although intracellular TNF alpha could not be detected in freshly isolated monocytes, both extracellular IL-1 and TNF alpha concentrations were greatly increased after 20 h of in vitro culture of monocytes in the absence of exogenous stimulation and in serum-free conditions. However, long-term haemodialysis patients showed higher values of secreted IL-1 than not-yet dialysed uraemic patients. During a single dialysis session a significant increase in both cell-associated and secreted IL-1 but not TNF alpha was observed in long-term haemodialysis patients. In contrast, no change in the concentration of either cytokine could be detected at the end of the first dialysis session in uraemic patients. Our findings strongly suggest that factors related to uraemia could be a sufficient signal to initiate intracellular IL-1 protein synthesis and TNF alpha release by monocytes, but that greater IL-1 release could be stimulated during the periodic haemodialysis procedure.

Cells, Cultured↗
PubMed1991

Establishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients: a randomized prospective study.

The present prospective study was conducted in order to establish the relationship between complement activation and stimulation of phagocyte oxidative metabolism observed in long-term hemodialysis (HD) patients during the early phase of dialysis with cellulosic membranes. Two groups of 10 randomized (HD) patients treated with cellulosic (Cuprophan, CUP) or synthetic polyacrilonitrile (PAN AN-69) membranes were studied. Leukocyte counts, C3a antigen plasma concentration and whole blood basal and stimulated chemiluminescence (CL) production were determined in blood samples drawn from the fistula before dialysis (T0) and from both the afferent and efferent lines of the dialyser at 15 min (T15) and at the end (Tend) of the dialysis session. This study confirms that, coincident with the nadir of leukopenia observed at T15, dialysis with CUP but not PAN membranes induces a marked rise in C3a antigen levels and profound alterations in whole blood CL production consisting of a dramatic increase in basal CL and a significant loss in CL response capacity to stimulating agents. It further demonstrates that a direct relationship exists between the variations in C3a antigen plasma levels and whole blood CL production observed in the CUP group of patients from T0 to T15 (delta 15) of dialysis. This relationship is characterized by a positive correlation between delta 15 C3a and delta 15 basal CL levels in afferent and efferent lines, and a negative correlation between delta 15 C3a and delta 15 CL response capacity values in the efferent but not afferent line. In contrast, no significant correlation with the type of dialysis membrane could be demonstrated between the variations in polymorphonuclear neutrophil counts and C3a antigen levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1990

Phagocyte oxidative metabolism in cyclosporine- or placebo-treated patients with insulin-dependent (type I) diabetes mellitus of recent onset.

Several lines of evidence suggest that phagocyte-mediated oxidative processes are involved in damage to pancreatic islet cells of Type I insulin-dependent diabetes mellitus (IDDM). This hypothesis, however, has not yet been explored at the clinical onset of IDDM. Similarly, the possibility that cyclosporine A (Cy-A) might exert a selective influence on these phagocyte-mediated oxidative reactions has also not yet been investigated as compared to a placebo. The present study tested both hypotheses in 32 patients with recently diagnosed IDDM who were part of the recent French multicenter randomized therapeutic trial of Cy-A. The production of reactive oxygen intermediates (ROI) by circulating polymorphonuclear (PMN) and mononuclear (MN) phagocytes was determined by luminol-dependent chemiluminescence (CL), both directly within microamounts of whole blood and in purified PMN or MN phagocyte suspensions. Lastly, CL production was measured in the absence (resting CL) and the presence of a panel of particular and soluble phagocyte membrane-stimulating agents. We found that on entry into the trial, i.e. within less than 2 months of the clinical onset of IDDM, patients had normal whole blood CL production in the absence of a stimulating agent and upon phagocytic challenge with latex or opsonised zymosan particles. By contrast, whole blood CL responses to soluble stimuli such as phorbol myristate acetate (PMA), concanavalin A (Con-A) and F Met-Leu-Phe (FMLP) were significantly higher than in the control group of 52 normal subjects (P less than 0.01). In purified PMN and MN phagocyte suspensions, both resting and stimulated CL productions were normal, regardless of the type of stimulating agent. After 3 months of treatment, whole blood CL responses to Con-A and FMLP returned to almost normal levels in patients treated with Cy-A (15 cases) but not in those receiving the placebo (17 cases); PMA-induced CL responses were also decreased, but this was found in both groups of patients. In purified phagocyte suspensions we detected no effect of Cy-A on PMN, whereas MN phagocytes from Cy-A-treated patients showed reduced CL responses to FMLP but not to other stimuli. Altogether, these results demonstrate for the first time that the capacity of circulating PMN and MN phagocytes to generate ROI is normal at the clinical onset of IDDM and suggest that circulating substances increase oxidative responses to soluble, but not particulate, stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Influence of uremia and hemodialysis on circulating interleukin-1 and tumor necrosis factor alpha.

Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) were determined in the plasma of long-term hemodialysis (HD) patients and uremic (UR) patients undergoing their first dialysis session using either cellulosic (CUP) or synthetic (PAN-AN 69) membrane-equipped dialyzers. In long-term HD patients, plasma IL-1 and TNF alpha levels were significantly increased compared to their levels in normal subjects. During a single dialysis session, a significant increase in IL-1 but not in TNF alpha was observed. In not yet dialyzed UR patients, IL-1 plasma levels did not differ from those observed in normal subjects. By contrast, TNF alpha was found significantly increased although less than in long-term HD patients. During the first dialysis session, no significant increase was observed in the levels of either monokine. Lastly, regardless of the group of patients, no significant influence of the dialysis membrane could be detected, suggesting that the observed changes are not exclusively secondary to the activation of complement. Altogether, these results suggest that the passage of the blood through the extracorporeal dialysis circuit triggers the secretion of IL-1 and further exacerbates that of TNF alpha by monocytes. The presence of increased TNF alpha in the plasma of first-dialysis UR patients suggests that factors unrelated to dialysis contribute to the activation of monocytes in these patients. Lastly, the concomitant presence of IL-1 and TNF alpha in the plasma of long-term HD patients could be responsible for some of the clinical features observed in these patients, and provides strong evidence favoring the concept that HD can be assimilated to a recurrent acute-phase inflammatory response.

Acrylic Resins↗
PubMed1989

Role of oxygen-dependent mechanisms in monoclonal-antibody-induced lysis of normal T cells by phagocytes. II. Murine phagocytes.

In the first part of this study, we reported that antibody-dependent cellular cytotoxicity (ADCC) mediated by human polymorphonuclear (PMN) and mononuclear (MN) phagocytes against anti-T-cell monoclonal-antibody-(mAb)-coated T lymphocytes, is mainly dependent upon the generation of reactive oxygen intermediates (ROI) for PMN, whereas MN-mediated ADCC depends on both oxidative and non-oxidative cytolytic events. Using mouse effector cells from various organs and at various maturation or activation states, the present report shows that in this ADCC model against mAb-coated normal T cells, resident spleen (SPC) and peritoneal exudate (PEC) cells selectively bound and developed oxidative responses to these mAb-coated normal target cells but remained ineffective in ADCC. Similar data were obtained with inflammatory recruited (thioglycollate-elicited or Biogel granuloma-induced) macrophages, whereas immunologically activated macrophages (from BCG-treated mice) mediated both strong oxidative responses and potent ADCC reactions. In contrast, and as in the human system, both resident (from bone marrow) and inflammatory PMN phagocytes exerted significant lysis of these mAb-sensitized normal lymphoid cells. These findings, which are similar to those reported in ADCC against tumour target cells, strongly suggest that the nature (normal or tumoral) of the target cell does not influence the lytic mechanisms of macrophage-mediated ADCC and that these latter require activated macrophages and, like PMN, involve strong (if not exclusive) ROI participation.

Animals↗