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Biomedical subjects

P Sheldon

Publications and source records attributed to P Sheldon.

At least 37 records · Page 2Linked to original sources

Comparison of the effect of oral sulphasalazine, sulphapyridine and 5-amino-salicylic acid on the in vivo antibody response to oral and systemic antigen.

1. Mice, whose drinking water contained sulphasalazine, sulphapyridine or 5-amino-salicylic acid, received an antigenic challenge by cholera toxin administered either orally or systemically. 2. Sulphasalazine treated mice made less specific antibody of IgA class provided the antigen also was administered orally (P = 0.009 for days 7-28). When the antigen was administered systemically, there was a vigorous anti-cholera toxin antibody response of IgG class, and a lesser IgM but only a weak IgA response. The effect of sulphasalazine in this case was confined to the IgG response, which was significantly suppressed on day 28 (P = 0.008). 3. Sulphapyridine and 5-amino salicylic acid had no significant effect on the anti-cholera toxin (CT) responses of all three classes. 4. It therefore appears that in this model, only sulphasalazine is capable of influencing the humoral immune system, the antibody class affected depending on the route of entry of antigen. This may have implications for conditions such as rheumatoid arthritis and chronic inflammatory bowel disease, for which sulphasalazine has been found useful.

Administration, Oral↗

Effect of sulphasalazine on antibody response to oral antigen.

Cholera toxin was orally administered to mice concurrently receiving sulphasalazine (SASP) dissolved in L-lysine, or a control substance (L-lysine alone). Circulating antibodies to cholera toxin of IgM, IgG and IgA class were determined by direct ELISA at day 7, 14, 21 and 28. Although both groups made a significant antibody response to the antigen, mice receiving SASP tended to produce lower levels. These were significant for IgA on day 21 (P = 0.013), and for days 7-28 (P = 0.009), and 14-28 (P = 0.007). Overall, considering all antibody classes together from day 7 to 28, there was a significant effect in the SASP treated group (P = < 0.04). It appears that SASP exerts a mild immunomodulatory effect on the mucosal immune system. Further work is obviously required to substantiate these findings. The effect on the gut mucosal immune system of a drug known to ameliorate rheumatoid arthritis may offer an insight into the aetiopathogenesis of this disease.

Administration, Oral↗

Adhesion of rheumatoid peripheral blood and synovial fluid mononuclear cells to high endothelial venules of gut mucosa.

Mononuclear cells isolated from paired blood and synovial fluid of seven patients with rheumatoid arthritis showed cytoadherence to porcine Peyer's patch high endothelial venules using the Stamper-Woodruff method. A significantly greater proportion of binding was found among the synovial fluid lymphocytes. These would appear to be a population of cells that share adherence characteristics with cells known to be of gut mucosal origin, suggesting that in rheumatoid arthritis some lymphocytes derived from mucosa migrate to joints.

Adult↗

Forces and torques produced by a 640-gauss permanent magnet of ferromagnetic objects.

Magnetic forces and torques were measured in a 640-G permanent magnet. The forces on external objects were directed in such a way and of such a strength that the likelihood of injury from unsupported ferromagnetic objects was very small. The forces and torques on ferromagnetic objects within the subject were comparable to those produced by gravitational and inertial efforts in daily living.

Equipment Safety↗

Oblique reformatting of multislice magnetic resonance images for improved visualization of coronary arteries.

A technique for reformatting multislice magnetic resonance images into arbitrary oblique planes has been developed and implemented on a Toshiba MRT-35 (formerly Diasonics MT/S) imaging system (South San Francisco, CA). This method is designed to allow the user to easily define a new plane by marking with a cursor features of interest on two or three different image levels. These features are combined in the resulting oblique image. The reformatted image can have arbitrary angulation and is created with a pixel dimension equivalent to the original data set. Resolution ranges from the original in-plane resolution to the slice thickness, depending on angulation. An improvement in signal-to-noise ratio results from the effective averaging performed by interpolation. This method is optimally used to correct for small variations in alignment, such as the positioning of the intervertebral disks. It can also be used to generate reformatted images at many different angles from a single multislice data set. This method has been applied to the particular problem of improving the presentation of coronary arteries on a conventional set of multislice spin-echo cardiac images by increasing the visible length of individual coronary segments.

Coronary Vessels↗

Electrophysiology of the central serotonin system: receptor subtypes and transducer mechanisms.

It is becoming evident that the diverse electrophysiological actions of 5-HT in the central nervous system can be best formulated in terms of receptor subtypes and their respective effector mechanisms. Based on the findings described in this review, the following pattern of central 5-HT electrophysiology is emerging: 1) inhibitory effects are mediated by 5-HT1 receptors linked to the opening of K channels via pertussis-toxin sensitive G proteins: 2) facilitatory effects are mediated by 5-HT2 receptors and involve the closing of K channels, an effect which appears to be negatively modulated by activation of the PI second messenger system: 3) fast excitations are mediated by 5-HT3 receptors, most likely involving a direct interaction with an ion channel rather than through coupling with a G protein or a second messenger. Further studies will be required in a wider range of brain areas to establish the generality of these conclusions.

Animals↗

"Angiography" by magnetic resonance imaging: detailed vascular anatomy without ionizing radiation or contrast media.

Using software to transform magnetic resonance imaging (MRI) tomographic data into three-dimensional projections, we have produced "angiograms" of the abdominal aorta in 18 patients with occlusive (15) and aneurysmal (3) disease. This information may be displayed to demonstrate flow, cross-sectional diameter, or aortic surface anatomy. To test the accuracy of the MRI studies, we compared them at selected points with the transected aorta and with routine aortograms. Relative cross-sectional diameter estimated by MRI was within 15% of measured aortic diameter in 14 of the 18 vessels and enabled correct detection of thrombus in 16. We conclude that MRI may accurately image the diseased abdominal aortic wall. In addition, an angiographic display format may aid in the interpretation of these studies. Although MRI is not likely to replace aortography, it could be used adjunctively to define aortic wall thickness and the presence of thrombus.

Aged↗

Identification of aortic thrombus by magnetic resonance imaging.

The unique properties of magnetic resonance imaging result in the potential to differentiate various components of the diseased arterial wall. In this article four cases are presented in which magnetic resonance imaging showed mural aortic thrombus and its anatomic relationship to the visceral and renal arteries. Once thrombus is identified and localized specific operative strategies can be undertaken to prevent recurrent embolic events and/or avoid perioperative thromboembolic complications.

Aged↗

Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes--clues to its clinical action?

The effects of sulphasalazine (SASP), sulphapyridine (SP), and 5-aminosalicylic acid (5-ASA) have been studied on mouse spleen cells cultured in the presence of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). SASP exhibited a significant degree of suppression, at doses in the range 25-100 micrograms/ml (p less than 0.01), this suppression being greater than 50% at 50 micrograms/ml. SP exhibited only a minor degree of suppression (10% at 75 micrograms/ml, p less than 0.01). Coadministration of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, produced no evidence of further suppression in the presence of SASP or SP. Administration of SP plus 5-ASA to parallel cultures that were profoundly suppressed by the molecular equivalent amount of SASP resulted in no suppression. This implied requirement of the intact parent molecule (SASP) to produce this effect, at these concentrations. The concentration of SASP required to produce more than 50% suppression was higher than that ever attained in the peripheral blood of humans receiving therapeutic doses of the drug. Human lymphocytes are similarly suppressed by SASP, but only at higher concentrations than are required for murine cells. Thus, if the parent drug is the active moiety and requires these concentrations to be effective in vivo, it follows that the site where these effects may be mediated is likely to be the intestinal tract. The effects described would suggest the gut associated lymphoid tissue as a likely target.

Aminosalicylic Acids↗