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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 271 records · Page 15Linked to original sources

Regulatory effects of IL-13 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.

Activated macrophages are central to the destructive processes of chronic inflammatory arthritis. In this study, it was hypothesized that IL-13, a product predominantly of 'Th2-type' lymphocytes, may be used therapeutically to down-regulate monocyte/macrophage activities at sites of chronic inflammation. Synovial fluid mononuclear cells were isolated from 12 patients with chronic inflammatory arthritis. Peripheral blood mononuclear cells (PBMC) were isolated at the same time as synovial fluid cells from all 12 patients. IL-13 significantly inhibited lipopolysaccharide (LPS)-induced tumour necrosis factor-alpha (TNF-alpha) production by mononuclear cells from peripheral blood, but not synovial fluid. In contrast, IL-13 inhibited LPS-induced IL-1 beta production by all cells, and as a positive response to IL-13, CD23 expression was increased on both cell populations. Blood monocytes cultured for 7 days with granulocyte-macrophage colony-stimulating factor (GM-CSF) or M-CSF responded to IL-13 in a manner similar to that detected for synovial fluid-derived cells, with suppression of LPS-induced IL-1 beta, but not TNF-alpha, production. In all experiments, the responses to IL-13 were very similar to those detected to IL-4, but differed from those measured with IL-10. Thus, the responses to IL-13 by synovial fluid cells and cultured monocytes are not equal to those of blood monocytes. The similar responses to IL-4 and IL-13 support claims of a common element for signalling from the IL-4 and IL-13 receptors. Furthermore, the activity of a common receptor chain may be altered by monocyte activation and differentiation.

Antigens, CD↗

The assessment of left ventricular filling dynamics using an online automatic border detection algorithm: comparison with cineventriculography.

An echocardiographic system has been developed that performs automatic endocardial border detection and instantaneously calculates and displays a waveform of left ventricular cavity area versus time. The purpose of this study was to compare measurements of left ventricular filling dynamics from automatic border detection echocardiography with similar measurements from cineventriculography. Thirty-three patients undergoing cardiac catheterization had automatic border detection echocardiography performed within 45 minutes of cineventriculography. Ten patients had normal catheterization findings and 23 had cardiac disease. The automatic border detection waveforms generated from two echocardiographic views were measured to determine the fraction of filling occurring during the early diastolic rapid filling phase and during the filling phase resulting from atrial contraction. Similar fractions were derived from curves generated from frame-by-frame measurements of cineangiographic volumes. Results were analyzed by correlating echocardiographic and cineventriculographic results, and by a limits of agreement analysis (limits of agreement were +/- 2 standard deviations of the mean difference between echocardiography and cineventriculography). There were significant correlations between echocardiography and cineventriculography for each of the parameters studied. The best results were obtained for the apical four-chamber view (rapid filling fraction r = 0.72, P < 0.0001, atrial filling fraction r = 0.56, P < 0.001). Differences in filling patterns between normal and abnormal patient groups detected by cineventriculography were also detected by automatic border detection echocardiography. However, broad limits of agreement were observed, that may limit the ability of the automatic border detection system to reliably predict cineventriculographic results in an individual patient. Automatic border detection echocardiography can provide information about left ventricular filling dynamics that is similar to that obtained from frame-by-frame analysis of cineventriculograms. However, the variability in the results may limit the application of the technique in individual patients.

Adult↗

Enzyme-linked immunosorbent assay (ELISA) using a glycolipid antigen for the serodiagnosis of melioidosis.

The serodiagnosis of melioidosis is commonly performed with tests using protein or polysaccharide as antigen. However, due to the low sensitivity, specificity and difficulty in the preparation of the antigens, more simple, precise and reproducible diagnostic tests were required. A purified glycolipid antigen (GL) which is a specific lipid component of Burkholderia pseudomallei has been used in an ELISA. With this antigen, specific immunoglobulin G (IgG) was detected in 49 out of 50 melioidosis sera. IgG was also detected in 2 out of 185 (Japanese) and 16 out of 181 (Vietnamese) control sera. Thus, the sensitivity was 98.0%, and specificity was 98.9% and 91.1% in the Japanese and Vietnamese sera, respectively. When the ELISA and indirect haemagglutination (IHA) tests were combined, a sensitivity of 100% and specificity of 97.8% were achieved. The advantages of the glycolipid antigen are ease of preparation, stability, high sensitivity and specificity.

Antigens, Bacterial↗

Postantibiotic effects and Burkholderia (Pseudomonas) pseudomallei: evaluation of current treatment.

The postantibiotic effects (PAEs) OF 16 antibiotics or antibiotic combinations currently used against Burkholderia (Pseudomonas) pseudomallei were determined. The beta-lactams had zero PAEs, while the carbapenems and ciprofloxacin induced median PAEs of 1 and 5 h, respectively. These results emphasize the need to maintain antibiotic levels above inhibitory concentrations in blood throughout the dosing interval in cases of severe melioidosis.

Anti-Bacterial Agents↗

In vitro antimicrobial susceptibilities of strains of Yersinia pestis.

The in vitro activities of 14 antimicrobial agents were determined for 78 strains of Yersinia pestis. The most active antibiotics were ceftriaxone and ciprofloxacin, followed by ofloxacin and ampicillin. The agents traditionally used for the treatment of plague (streptomycin, tetracycline, and chloramphenicol) were considerably less active. Azithromycin showed poor activity against all strains.

Anti-Bacterial Agents↗

Latex agglutination for rapid detection of Pseudomonas pseudomallei antigen in urine of patients with melioidosis.

A latex agglutination test for the detection of Pseudomonas pseudomallei antigen in urine was evaluated for the rapid diagnosis of melioidosis. With unconcentrated urine, antigen was detected in only 18% of patients with melioidosis overall. However, when urine was concentrated 100-fold, antigen was detected in 47% overall and in 67% of patients with septicaemia or disseminated infection, in whom a rapid diagnosis is most important. The specificity of the test was 100%. These results compared favourably with an enzyme immunoassay. This latex agglutination test is a simple, rapid and highly specific method of diagnosing melioidosis, and will be particularly useful in areas with limited laboratory facilities.

Antigens, Bacterial↗

Detection of C-polysaccharide in serum of patients with Streptococcus pneumoniae bacteraemia.

AIM: To investigate the fate of Streptococcus pneumoniae C-polysaccharide antigen in serum in patients with S pneumoniae bacteraemia. METHOD: In vitro dissociation experiments were performed to demonstrate that C-polysaccharide was masked by ligands in normal and acute phase serum. Serum samples from 22 patients with S pneumoniae bacteraemia were treated to dissociate immune complexes and then tested for C-polysaccharide by enzyme linked immunosorbent assay (ELISA). RESULTS: C-polysaccharide antigen was masked in normal and acute phase serum but could be released by EDTA treatment and detected by ELISA. Antigen was found in six patients ranging in concentration from 2.5 to 200 ng/ml. Patients with detectable antigen were more likely to die than those in whom antigen was not detected. CONCLUSION: This study demonstrates that C-polysaccharide antigen commonly circulates in patients with S pneumoniae bacteraemia but its presence is masked by ligands present in serum.

Acute Disease↗

Poly(vinyl chloride) formulations: acute toxicity to cultured human cell lines.

Two quantitative cytotoxicity assay methods (cytoplasmic retention of carboxyfluorescein and mitochondrial cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)) have been used to evaluate the response of two cultured human cell lines; HepG2 (hepatoma) and W138va13 (transformed lung fibroblasts) to extracts of a range of poly(vinyl chloride) (PVC) formulations. Two plasticizers; di(2-ethylhexyl)phthalate (DEHP) and di-isooctyl phthalate and a range of tin and non-tin stabilizers were incorporated in the study. Only those formulations containing both a plasticizer and a tin-based stabilizer produced extracts which were toxic. Extracts of those formulations which contained both plasticizer and dibutyl tin dimaleate stabilizer were toxic to both cell lines in both assay methods. Extracts of a formulation containing plasticizer and a dioctyl tin mercaptide were toxic to both cell lines in the carboxyfluorescein assay but were only toxic to the WI38va13 cells in the MTT assay. The WI38va13 cells were generally more sensitive to the extracts than the HepG2 cells. When serial dilutions of the extracts were evaluated, the carboxyfluorescein assay proved to be the more sensitive of the two. The acute toxicity of extracts of these PVC formulations cannot be directly attributed to the plasticizers or to the tin stabilizers. It is likely that a synergistic mechanism, such as plasticizer facilitated extraction of the tin stabilizer, exists.

Carcinoma, Hepatocellular↗

Improved hepatocyte in vitro maintenance in a culture model with woven multicompartment capillary systems: electron microscopy studies.

Primary pig hepatocytes form a tissuelike structure in an in vitro culture model that has provision for three-dimensional cell orientation, cell aggregation, decentralized cell perfusion with low metabolite gradients, integral oxygenation, and nonparenchymal cell coculture. Scanning electron microscopy (SEM) has shown that hepatocytes spontaneously form aggregates in a three-dimensional structure between and on the surface of artificial capillaries. Transmission electron microscopy (TEM) has shown that after 7 weeks of in vitro perfusion, the cell ultrastructure remains similar to that of the parenchyma in vivo. Golgi complexes, active membrane processes, reorganization of cell junctions, and bile canaliculi-like intercellular spaces were demonstrated.

Animals↗

Cervical radiculopathy: causes and surgical treatment.

This article discusses the basic pathological, anatomical, and clinical problems associated with the herniated cervical disc or degenerative cervical disc disease and provides an overview of the common surgical approaches to the operative treatment of this common degenerative disorder.

Adult↗

Comparison of the suppressive effects of interleukin-10 and interleukin-4 on synovial fluid macrophages and blood monocytes from patients with inflammatory arthritis.

This study determined the potential capacity of interleukin-10 (IL-10), compared with IL-4, to control the production of tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-1 receptor antagonist (IL-1ra) and the expression of major histocompatibility complex (MHC) class II antigens by monocytes/macrophages isolated from synovial fluid of patients with rheumatoid or other forms of chronic inflammatory arthritis. Mononuclear cells were isolated from synovial fluid and peripheral blood and incubated with or without lipopolysaccharide (LPS), and with or without IL-10 (100 U/ml, 10 ng/ml) or IL-4 (10 ng/ml) for 22 hr. TNF-alpha, IL-1 beta and IL-1ra levels were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants, and MHC class II expression was examined on the monocytes/macrophages by flow cytometry. IL-10, unlike IL-4, decreased TNF-alpha production by LPS-stimulated synovial fluid cells to the same extent as by LPS-stimulated peripheral blood cells from the same patients. IL-10 and IL-4 suppressed equally IL-1 beta production by the same cells. However, only IL-4 significantly increased IL-1ra production by synovial fluid mononuclear cells. Synovial fluid cells expressed increased levels of MHC class II antigen, and these levels were not as efficiently suppressed by IL-10 as they were for peripheral blood cells. Because IL-10 and IL-4 differentially regulate TNF-alpha and IL-1ra production by synovial fluid mononuclear cells, selective use of either IL-10 or IL-4 in the treatment of chronic inflammatory conditions will depend on whether TNF-alpha or IL-1, respectively, is established as primarily responsible for the maintenance of the chronic inflammatory condition.

Arthritis↗