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Biomedical subjects

T E Miller

Publications and source records attributed to T E Miller.

At least 109 records · Page 6Linked to original sources
PubMed1983

Infection-induced immunosuppression in pyelonephritis: characteristics of the suppressor cell(s).

Infection-induced suppressor cells may be associated with a depression of cell-mediated immune (CMI) mechanisms in pyelonephritis. In the present study, cell viability and cell to cell contact were established as prerequisites for immunosuppression and the role of mononuclear phagocytic cells and polymorphonuclear leukocytes, as immunoregulatory cells affecting CMI, was also examined. Fractionation of spleen cell suspensions was carried out using carbonyl iron, nylon wool, glass beads, and sephadex. These procedures restored mitogenic responsiveness to splenic lymphocytes from pyelonephritic animals, and it was possible to isolate cells with accessory and suppressor activity from nylon wool columns. Elutable cells (that is, cells which adhere to the column but could be recovered by the addition of EDTA) were characteristically accessory cells and increased the mitogenic responsiveness of normal lymphocytes. Adherent splenocytes which suppress mitogenic responses were isolated from pyelonephritic animals. Additionally, neutrophils, at concentrations readily demonstrable in lesions, depressed CMI responses in vitro. With this information available it should now be possible to carry out a detailed analysis of the cellular mechanism by which CMI in renal infection is depressed.

Animals↗
PubMed1983

Host immune status in uremia. IV. Phagocytosis and inflammatory response in vivo.

Infection is a frequent complication and cause of death in renal failure, but the association between uremia, depressed immune status, and susceptibility to infection is far from proven. In the present studies, the effect of uremia on the inflammatory response and phagocytic ability was investigated in an animal model. The inflammatory response, as measured by the ability of leukocytes to mobilize into subcutaneous implanted sponges, was impaired at 6 hr but was normal 24 hr after implantation. The peripheral blood response of uremic animals to the leukocytosis promoting protein from Bordetella pertussis was similar to that of control animals. Reticuloendothelial clearance of labelled albumin was unimpaired but catabolism of this substance was reduced significantly in uremic animals. The ability of the uremic host to clear an intravenous challenge of virus was also depressed. Phagocytic and bactericidal capability of polymorphonuclear (PMN) leukocytes, measured in vitro by latex ingestion and phagocytosis and killing of Staphylococcus aureus, was normal. PMN phagocytic function in vivo was determined by the clearance of viable Escherichia coli from subcutaneously implanted sponges and no significant difference between control and uremic groups was found. These studies have further defined the effect of uremia on immune mechanisms and support our contention that uremia per se is not a major factor contributing to the compromised immune status in this host.

Animals↗
PubMed1982

Anti-inflammatory activity in fractionated extracts of the green-lipped mussel.

The New Zealand green-lipped mussel (Perna canaliculus) is the source of a para-pharmaceutical called Seatone. Claims have been made that the preparation may be helpful in the management of inflammatory joint disease but results of clinical studies to date have been contradictory. An earlier experimental study demonstrated anti-inflammatory activity in the crude preparation and further experiments to isolate and characterise the active fraction were indicated. A two-step fractionation procedure resulted in an extract, which although only 16 percent by weight of the parent material, retained anti-inflammatory activity. Experiments involving alternative routes of administration, with heat or enzyme treatment of the active extract and a comparative analysis of fractions from related bivalves, all demonstrated that the anti-inflammatory effect was genuine and did not result from counter-irritancy. The initial results suggest that the active agent is a proteinaceous macromolecule.

Administration, Oral↗
PubMed1982

Synergism between immunosuppressive agents and uremia?

The susceptibility of uremic patients to infectious disease has been widely reported, but the host immune factors associated with the increased incidence of infection have not been clearly defined. In this study, the possibility of synergism between biologically active components that accumulate in uremia and immunosuppressive drugs used in the course of management was investigated. An animal model of chronic stable uremia was used in these experiments to assess the effect of cyclophosphamide, methotrexate, and azathioprine on antibody response in the uremic host. Chronic uremia did not affect the immunosuppressive activity of cyclophosphamide, methotrexate, or azathioprine, and synergism between these agents and uremic components is unlikely to complicate further the immune status of the host in renal failure.

Animals↗
PubMed1981

Clinical significance of anti-double-stranded DNA antibodies detected by a solid phase enzyme immunoassay.

A solid phase enzyme immunoassay (EIA) detected anti-double-stranded (ds) DNA antibodies in 88% of sera from patients classified clinically as having active systemic lupus erythematosus (SLE) without renal symptoms and 93% with renal disease. Fifty-six percent of sera from patients with inactive SLE were EIA positive for anti-dsDNA antibodies. The EIA had a sensitivity and specificity comparable to radioimmunoassay (RIA) and hemagglutination for patients with active SLE with or without renal disease, but it detected anti-dsDNA antibodies more frequently in patients with inactive SLE than the latter procedures. Precipitating antibodies detected by counterimmunoelectrophoresis (CIE) were less common in patients with renal disease (23% incidence) than clinically active patients without renal disease (79% incidence). Twenty-four SLE sera with elevated levels of C1q binding showed a 96% concordance for a positive EIA for anti-dsDNA antibodies in contrast to 66% concordance by RIA or hemagglutination. These findings suggest that the EIA is a sensitive and specific method for detection and measurement of anti-dsDNA antibodies. Several clinical applications of the EIA are discussed.

Antibodies, Antinuclear↗
PubMed1981

Evaluation of cefoxitin nephrotoxicity in experimentally induced renal failure.

The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.

Animals↗
PubMed1980

The anti-inflammatory activity of Perna canaliculus (NZ green lipped mussel).

The anti-inflammatory effect of a crude fraction of the New Zealand green lipped mussel (Perna canaliculus) has been investigated. A carrageenan-induced inflammatory oedema of the rat hind footpad was used as the experimental model. Non-steroidal anti-inflammatory agents were first shown to be capable of reducing the inflammatory oedema and in the subsequent experiments a representative agent was included as a reference substance. The preparation, Perna canaliculus, effectively reduced the footpad oedema but only if injected into the peritoneal cavity. Decreasing amounts were given IP and 500 mg/kg of the crude preparation was found to be the lowest single dose that would produce a significant reduction in the inflammatory response to carrageenan. Lower doses were effective if the substance was first administered daily for several days, prior to the challenge. Oral administration was not effective in reducing the inflammatory response.

Administration, Oral↗
PubMed1980

Role of complement in chemotaxis: study of a localized infection.

A model of Escherichia coli-induced pyelonephritis was used to study the effect of complement depletion in an organ-specific, nonimmunological inflammatory lesion in rats. In this model of a local infection, which can be considered to be nonspecific inflammatory stimulus, the depletion of complement by the administration of a purified cobra venom factor did not alter the course of the disease. There were minor differences when the results from complement-depleted and normocomplementemic animals were compared, but the composition of the inflammatory infiltrate was not greatly altered. Therefore, the presence of C3 and a functional complement system are relatively unimportant factors in determining the characteristics of the inflammatory response in a localized infection-induced lesion.

Animals↗
PubMed1980

Host immune status in uraemia. I. Cell-mediated immune mechanisms.

An experimental model of stable uraemia has been used to determine the effect of uraemia on cell-mediated immune mechanisms in the rat. Controlled resection of renal tissue allowed the establishment of a 'moderate' (blood urea 100-200 mg/100 ml) and 'severe' grade of uraemia (BU > 200 mg/100 ml). The immune responsiveness of isolated lymphocyte suspensions from uraemic animals was similar to that of sham-operated animals but lymphocyte function in both groups was suppressed compared with control non-manipulated animals. This was particularly evident in the graft vs host reaction. The host vs graft which assumes the cell-mediated immune status in the live animals, was also depressed in the uraemic animals but in contrast to the previous results sham-operated animals exhibited normal responses. The results underscore the importance of surgically induced anergy as a factor complicating the assessment of immune function in uraemia and may explain some of the inconsistencies observed in the evaluation of cell-mediated immunity by in vitro analysis of lymphocyte suspensions and tests of immune function in the intact host.

Animals↗
PubMed1980

Host immune status in uraemia III. Humoral response to selected antigens in the rat.

The humoral immune status of patients with uraemia is controversial. In the present experiments a carefully defined animal model, in which a chronic state of moderate and severe uraemia was induced, has been used to resolve conflicting views. The capacity of the uraemia host to respond to immunogenic stimulation was assessed by challenging uraemic animals with bacterial, viral, T cell-dependent and T cell-independent antigens. The experiments have shown that the immune responsiveness of animals with chronic severe uraemia, immunized with sheep red blood cells, Escherichia coli 075, keyhole limpet haemocyanin and phi X174 bacteriophage is comparable to those found in sham-operated and control groups. The results strongly suggest that uraemia per se does not affect the ability of the host to respond to a wide range of antigenic stimuli. This conclusion is important in that it provides a basis for assessing further the immune status of the uraemic host. If uraemic patients do have an immune deficit, one possible explanation is that uraemia potentiates the immunosuppressive activity of some drugs used in the clinical management of these patients.

Animals↗
PubMed1980

Host immune status in uraemia. II. Serum factors and lymphocyte transformation.

A model of experimentally induced uraemia has been used to study the effect of serum from uraemic rats on the immune responsiveness of thymus-derived (T) lymphocytes. Splenic lymphocytes from normal or uraemic animals responded to mitogenic stimulation with concanavalin A to a similar degree when cultured in a tissue culture medium containing the maximum non-toxic concentration of normal or uraemic serum in the culture system (3%). Serum from uraemic animals, however, had an immunosuppressive effect if the serum was first dialysed for 24 hr before being added to the tissue culture medium. When an alternative vessel was used which allowed the concentration of serum in the medium to be increased to 10%, serum from severely uraemic animals markedly suppressed the capacity of lymphocytes from normal animals to respond to Con A. Thus while serum from uraemic animals can be shown to be immunosuppressive, the results of the experiments are influenced by the conditions in vitro. The type of culture vessel and the concentration of serum in the culture medium are particularly critical determinants. It is likely that variations in laboratory procedures have contributed to the differences of opinion on the effect of serum from uraemic individuals on lymphocyte function.

Animals↗
PubMed1979

Studies on the specificity and clinical correlation of antiribosomal antibodies in systemic lupus erythematosus sera.

The specificity of antibodies reactive with cytoplasmic ribosomes detected in systemic lupus erythematosus (SLE) sera was studied by a radioimmunoassay procedure with 3H labeled HeLa cell polysomes. The antibodies were directed primarily against RNA or a ribosomal RNA-protein complex (rRNP). Anti-RNA antibodies exhibited comparable reactivity with ribosomal RNA, nuclear RNA, structural RNA, and a slightly lower degree of reactivity with low molecular weight RNA. Anti-rRNP antibodies may be detected by precipitation in agar gel and appear to require both the RNA and protein moieties of ribosomes for reactivity. SLE sera containing only anti-rRNP antibodies are limited to patients with active disease. Sera from patients with both active and inactive SLE contain either anti-RNA or a mixture of anti-RNA and anti-rRNP antibodies. The possible participation of anti-ribosomal antibodies in immune complex formation is discussed.

Antibodies, Antinuclear↗
PubMed1979

Peritoneal exudate T lymphocytes with specificity to sheep red blood cells. I. Production and characterization as to function and phenotype.

T lymphocytes which mediate DTH reactions to sheep red blood cells (SRBC) in mice enter casein-induced peritoneal exudates from which they can be recovered and assayed in a passive transfer system. Peritoneal exudates need not contain specific antigen for inducement of T-cell immigration. The amount (or biological activity) of DTH-transferring peritoneal exudate lymphocytes is enhanced by the previous use of immune modulating agents, such as cyclophosphamide (Cy) (200 mg/kg 2 days prior to sensitization), or BCG (10(7) live organisms i.v. 14 days prior to sensitization). SRBC-specific peritoneal exudate lymphocytes phenotypically are Thy 1+ and Ly 1+, 2-. In vivo, peritoneal exudate T cells from Cymodulated donors persist in circulation for a short period only and are subject to the suppressive mechanisms acting in anergic mice. Cells from BCG-plus-Cy-modulated donors, on the other hand, persist in circulation for a longer period and appear to be less susceptible to immune suppression.

Animals↗