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Biomedical subjects

B D Williams

Publications and source records attributed to B D Williams.

142 records · Page 8Linked to original sources

Circulating immune complexes after repeated halothane anaesthesia.

A patient developed hepatitis after receiving three halothane anaesthetics in 22 days. Twenty-four hours after the onset of jaundice she developed an acute serum sickness syndrome with polyarthralgia, proteinuria, and transient impairment of renal function. Serum concentrations of complement components C1q, C4, and C3 were substantially reduced, and immune complexes capable of activating the complement system via the classical pathway were present in the serum and synovial fluid. A metabolite of halothane was associated with these complexes. Fourteen months after exposure to halothane her lymphocytes were stimulated in vitro by this metabolite. The conditions under which stimulation occurred were unusual--namely, a 7S fraction of the serum, presumably IgG, was necessary. Our results provide strong evidence that halothane may be immunogenic and that its immunogenicity is dependent on the non-covalent binding of one of its metabolites to plasma proteins.

Anesthesia↗

Immune complexes in Behçet's syndrome and recurrent oral ulceration.

Seventeen patients with Behçet's syndrome, 11 with recurrent oral ulceration, and eight controls were studied in an investigation of the part possibly played by immune complexes in the transition from focal oral ulceration to the multifocal syndrome. Changes in the distribution of C3 within the first peak of Sephadex G200 fractionated plasma were found in nine of the 17 patients with Behçet's syndrome (55%), three of the 11 patients with recurrent oral ulcers, and none of eight controls. These findings provide indirect evidence that immune complexes are found in the plasma of these patients. Immune complexes were more common in patients with the neuro-ocular type of Behçet's syndrome than in those with the mucocutaneous type, and in those with herpetiform ulcers than in those with major or minor aphthous ulcers. Immune complexes were also associated with active disease. These findings support the hypothesis that the formation of immune complexes is an important step in the pathogenesis of Behçet's syndrome.

Antigen-Antibody Complex↗

Circulating immune complexes and symptoms in Hodgkin's disease.

Increased quantities of the third component of complement (C3) were found in the macromolecular fractions of plasma from patients with untreated Hodgkin's disease (H.D.) These changes provide indirect evidence that immune complexes are present in the plasma of patients with this disease; their presence is closely correlated with the symptoms of night sweats and fever which are associated with a poor prognosis. It is suggested that the detection of circulating complexes may help in assessing the severity of H.D.

Antigen-Antibody Complex↗

Disease activity in the nephritis of systemic lupus erythematosus in relation to serum complement concentrations. DNA-binding capacity and precipitating anti-DNA antibody.

Serum C4 and C3 concentration and binding of double-stranded-DNA (ds-DNA) were measured in sera from ninety-nine patients with systemic lupus erythematosus and clinical evidence of nephritis. C3 and C4 concentrations correlated poorly with ds-DNA binding. In sera from fifty-three patients, precipitating antibody was sought using the counterimmunoelectrophoretic technique. Precipitating antibody was detected on at least one occasion in 44% of the patients, and these sera with precipitating antibody showed higher binding of ds-DNA and lower C4 concentrations than those without precipitating antibody. In thirty-two patients, serial assessments of the activity of the renal disease were made using decline or improvement in glomerular filtration rate, degree of proteinuria, oedema and hypertension as indices of "activity". All patients were receiving immunosuppressive drugs. Active nephritis was rarely found in patients showing, at that time, a normal serum C4 or normal ds-DNA binding; but a raised ds-DNA binding or lowered serum C4 were found in both active and inactive nephritis. There was no correlation of activity with serum concentrations of C3, or the presence or absence of precipitating antibody. We conclude that measurements of serum-complement concentrations and binding of ds-DNA are of most use in the diagnosis of systemic lupus erythematosus, and that in patients with nephritis and taking immunosuppressive drugs, these tests are of limited use in guiding treatment.

Antibodies, Antinuclear↗

Immunoconglutinins and C3 in human saliva.

High titres of immunoconglutinin activity (antibody to bound complement components) have been found in the parotid, sublingual and submandibular saliva of most healthy subjects. The immunoconglutinin (IK) titre in mixed saliva was substantially lower than in the other samples of saliva. C3 was detectable in only three of 164 samples of parotid, submandibular and sublingual saliva but was present in forty-seven of 117 mixed saliva samples. It is suggested that crevicular fluid is the major source of C3 in mixed saliva. A negative correlation was found in mixed saliva between the C3 concentration and the IK titre, and this suggested that C3 was the inhibitor of IK in mixed saliva. Binding of C3 to IK has been demonstrated in mixed saliva by using highly purified salivary IK and C3. Purified C3, C3i, C3c and C3d inhibited the activity of purified IK. It is suggested that salivary IK represents the secretion of a B-lymphocyte population which has evaded the mechanism responsible for inducing B-cell tolerance to autologous serum proteins. The reason for its persistence in the salivary glands, however, is not known at present.

Adolescent↗

Urinary excretion of C3 antigen in glomerulonephritis.

C3 and fibrin degradation products (F.D.P.) have been measured in early morning urine samples from 38 normal people and 123 patients with glomerulonephritis. Normal urine contained less than 0.3 mug of either antigen per ml. C3 and F.D.P. were both detected in the urine of many patients with glomerulonephritis. Levels above 1 mug/ml were exceptional in patients with "minimal change," and the highest excretion of both antigens occurred in mesangiocapillary glomerulonephritis, membranous nephropathy, and focal glomerulosclerosis.Both C3 and F.D.P. excretion showed considerable variation with time, with parellel fluctuations in the two antigens. These fluctuations did not depend on the total protein leakage and suggest that the complement and clotting sequence are closely related in these glomerular disorders.

Antigens↗

Oral branched-chain amino acids decrease whole-body proteolysis.

BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

Adult↗

Effect of liposome surface charge on the stability of technetium (99mTc) radiolabelled liposomes.

Using liposomes radiolabelled by the 99mTechnetium-stannous chloride technique we have investigated the effect of surface charge on the stability of the isotope in vitro and in vivo. Dialysis of 99mTc-labelled positive, negative and neutral liposomes, which had been incubated in either saline or normal rat serum showed no significant loss of the isotope from the liposome surface with only 2 per cent of the isotope dialysed. A comparison of gel chromatography with dialysis confirmed that most of the isotope remained attached to the liposome surface, but it did reveal greater loss of the isotope, between 15 and 23 per cent. The liposome clearance rates obtained from 125I-egg phosphatidylcholine (EPC) and 99mTc dual-labelled positive or neutral liposomes were significantly different. The 99mTc marker was cleared five times faster from the positive liposomes and twice as fast from the neutral liposomes as the 125I-EPC integral membrane marker. The 99mTc attached to liposomes with a negative surface charge was stable in vivo and had the same clearance rate from the circulation as the 125I-EPC marker. These results indicate that the commonly used in vitro techniques for assessing liposome radiolabel stability are unsuitable for predicting the stability of the 99mTc in vivo.

Animals↗

High performance liquid chromatographic analysis of liposome stability.

Two techniques have been studied for their suitability for the analysis of the stability of liposomes: (1) High Performance Gel Permeation Liquid Chromatography (HPGPLC), a TSK G5000PW Ultrogel column; (2) Gel Permeation Chromatography (GPC), a Sepharose 4B column. The stability of dual radio-labelled, cholesterol-poor and cholesterol-rich, negatively charged liposomes in vitro (in saline and in serum), and in vivo, have been investigated using these two techniques. The HPGPLC TSK G5000PW column proved to be the superior technique for the analysis of liposome stability with the advantages of rapid run times, increased sample recovery, and smaller sample volumes were required. The results obtained confirm that inclusion of a high ratio of cholesterol into the liposome structure prevents phospholipid loss when exposed to serum, and that the cholesterol-poor liposome structure is dramatically altered under the same conditions. In conclusion, the TSK G5000PW column is ideal for monitoring movement of phospholipid between liposomes and serum proteins and for detecting changes in liposome size.

Animals↗

The direct separation of the diastereoisomers and enantiomers of the fungicide triadimenol by micellar electrokinetic capillary chromatography.

The direct chiral separation of the four enantiomers of the systemic fungicide triadimenol has been investigated using micellar electrokinetic capillary chromatography (MECC) with cyclodextrin (CD) chiral selectors and organic modifiers. The capillary operating temperature, applied voltage, and column diameter were all shown to be important factors in achieving an enantioselective separation. The addition of various CDs to the micellar buffer mixture was evaluated. The type of CD and its concentration affected the degree of separation, with the best separation of the enantiomers demonstrated for heptakis 2,6-di-O-methyl-beta-cyclodextrin (di-OMe-beta-CD). The addition of organic modifiers and CDs to the background electrolyte further enhanced separation. The best separation of the four enantiomers was obtained using an MECC buffer system consisting of 20% methanol, 0.02 M hydroxypropyl-beta-cyclodextrin (HO-Pr-beta-CD), and 0.05 M sodium dodecyl sulfate (SDS) in 0.02 M sodium borate and 0.02 M disodium hydrogen phosphate. The reported method demonstrates how the separation of enantiomers can be achieved by systematically varying the parameters in an MECC buffer system.

Capillary Action↗