Biomedical subjects
Publications and source records attributed to J R Baker.
'Wet vent', the principal clinical sign of which is diarrhoea, is common in budgerigars. In a survey of 83 cases examined post mortem 21 causes were found. The most common causes were enteritis, mainly of a non-infectious nature (18 cases), 'going light' (15 cases), abnormal gizzard structure (nine cases) and nephrosis (six cases).
Natural killer cells (NK) are important in immune surveillance, and they have found to be decreased in the serum of patients with various types of malignancies. In patients with thyroid carcinoma, we investigated NK activity of peripheral lymphocytes directed against either a standard tumor cell target, K562, or against the clinically relevant target cell, the thyrocyte. Although NK-cell activity was normal when directed against K562 cell targets, NK-cell activity was reduced when labeled thyrocytes were used as target cells. At effector to target cell ratios of 100:1 and 20:1, there was 43 +/- 3% (n = 7) and 29 +/- 3% (n = 7) lyses of thyrocytes using normal lymphocytes, and 17 +/- 4% (n = 5) and 13 +/- 2% (n = 3) using lymphocytes from patients with thyroid carcinoma. These findings suggest that NK-cells have distinct subpopulations and that immune surveillance against specific thyrocyte target cells may be important in thyroid cancer.
We investigated the contribution of albumin to serum fructosamine activity. On gel exclusion chromatography, pooled diabetic and pooled non-diabetic sera before and after incubation with [14C]glucose differed in fructosamine activity and radioactivity mainly in the albumin-containing fractions. We confirmed the major contribution of glycated albumin to serum fructosamine concentration using affinity chromatography on Blue Sepharose. The importance of high molecular mass species was further demonstrated by the recovery of reducing activity following dialysis and charcoal treatment. Fructosamine measurements in diabetic patients were not correlated with serum albumin concentration in individuals with urinary albumin less than 1 g/l. We conclude that fructosamine activity is a convenient measure of glycosylprotein concentration and that the index responds mainly to glycation of albumin. However, routine correction for serum albumin concentration is inappropriate.
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Guinea pig fat cell membranes (FCM) have been widely used in preference to thyroid membranes as a source of TSH receptors to investigate TSH receptor antibodies in Graves' disease, because FCM are ostensibly free of other thyroid antigens. However, by FCM immunoblotting we have found: 8 of 10 normal sera bound to determinants at 38 and 190 kDa; 17 other determinants were recognised by 60% of Graves' or Hashimoto sera and by 20% of normal sera; three determinants at 65-90 kDa were recognised by 5 of 13 Graves' but by none of the normal or Hashimoto sera; and none of the determinants recognised appeared to be related to the TSH receptor.
Antitumor drugs, like any other therapeutic agent, have the ability to incite hypersensitivity reactions. Certain of such drugs (e.g., L-asparaginase and taxol) cause reactions with great enough frequency to be a major impediment to repetitive use of the drug. Very few antitumor drugs have not had at least one reported instance of causing a hypersensitivity reaction. Most reactions are of the type I category in the Gell and Coombs classification, but there also are instances of types II, III, and IV reactions caused by many of the antineoplastic agents. The mechanisms of such reactions have been poorly evaluated in many reports. In analyzing a hypersensitivity reaction in a patient being treated for cancer, one should document that the antitumor drug is indeed the offender, and not an ancillary drug or a formulation product that is being used. There are many tests that evaluate the source and mechanism of hypersensitivity reactions. This article reviews the current information on hypersensitivity reactions to antineoplastic drugs and provides a logical approach for their assessment.
Thyrocytes from normal and goitrous portions of the thyroid gland from a patient with an enormous (635 gm) goiter were cultured in media, and their relative abilities to uptake thymidine, synthesize DNA, and secrete Tg and T4 were assessed. Tg, T4 and the ratio Tg/T4 in media at 72 h were 120 micrograms/dl, 1.6 micrograms/dl and 75 for normal cells, and 410 micrograms/dl and 273 for goitrous cells. DNA synthesis was 30-100% greater in goitrous than normal cells over a period of 72 h indicating abnormally high rates of cell division and growth, but their thymidine uptake was only 20% of that in normal cells. TSH elicited stimulation of thymidine uptake and DNA synthesis both in goitrous and in normal cells, but to a lesser extent in goitrous cells. No evidence of growth stimulating autoantibody activity was detected in the patient's serum. These data indicate that although the ability of goitrous cells to uptake thymidine was impaired, their DNA synthesis was more active than normal thyroid, which may have led to disordered cell growth as evidenced by the enormous goiter size in this patient. Although goitrous cells secreted more than three times as much Tg into media compared to normal, media T4 levels were similar, indicating an increased synthesis yet low iodination of Tg in goitrous cells. There does not appear to be any support for TGSI mediation of the goiter in this patient, but rather, the goiter may have been due to an intrinsic alteration in DNA synthesis resulting in vigorous cell growth.
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Autoimmune thyroid disease in man is commonly associated with autoantibodies against thyroglobulin, microsomes, and the TSH receptor, and the character and specificity of these antithyroid antibodies have been extensively utilized in investigating these conditions. In the present study we have asked whether other thyroid-related antigens exist, against which autoantibodies may be directed. A crude thyroid extract was separated by polyacrylamide gel electrophoresis followed by immunoblotting with serum obtained from patients with Graves' disease or Hashimoto's thyroiditis. Antibodies in sera from patients with Graves' disease and Hashimoto's thyroiditis reacted with many antigenic determinants in immunoblots of the thyroid membrane preparation (2000g supernatant). These determinants were disease specific in that sera from normals and patients with Addison's disease and rheumatoid arthritis did not react, but there was no difference between the patterns of reactivity with Graves' disease or Hashimoto's thyroiditis sera. Thyroglobulin produced two predominant bands of reactivity at 320 and 200 kDa, whereas purified microsomal antigen produced a triplet of bands around 105 kDa, when these preparations were reacted with appropriate autoimmune sera. Nonetheless, some sera produced additional bands with the microsomal antigen blots, indicating that some of the antigens which were detected using crude thyroid membrane remained in the microsome preparation to produce multiple antibody binding reactivities. We were unable to inhibit any of the antibody binding with TSH. Purification of individual thyroid antigens on the basis of their molecular weights should standardize current antibody assays and permit more detailed evaluation of the cellular immune responses in Graves' disease and Hashimoto's thyroiditis.
A method is described for the X-ray microanalysis of calcium pyroantimonate precipitates in smooth muscle using an electron microscope. Stimulation of calcium influx through voltage-operated channels using KCl and blockade of this effect with nifedipine were used to validate the method. Significant changes in the calcium content of rat renal artery were detected when osmium tetroxide-pyroantimonate were used as fixatives, whereas addition of glutaraldehyde yielded unsatisfactory data. Some effects of hydralazine are also briefly described.
The induction characteristics of propofol 2.0-2.5 mg kg-1 were compared with those of thiopentone 4-5 mg kg-1 in 60 fit children aged between 3 and 16 yr. All patients received i.m. premedication with papaveretum 0.4 mg kg-1 (maximum dose 15 mg) and hyoscine 0.008 mg kg-1 (maximum dose 0.3 mg). Seven children (24%) complained of pain after injection with propofol, compared with three (10%) after thiopentone. No child in either group complained of severe pain. Excitatory effects were observed in 10 children (33%) receiving propofol as opposed to five children (16%) after thiopentone, but these were transient and minor and all occurred after completion of injection. Apnoea lasting longer than 30 s occurred in only four children (13%) in each group despite the use of opioid premedication. The mean duration of apnoea was similar in both groups. Propofol caused greater decreases in arterial pressures (systolic, diastolic, mean) than thiopentone, but only the difference in systolic arterial pressure achieved significance. There was a significant difference in heart rate, which did not change after propofol, but increased with thiopentone. The overall quality of induction was assessed as being good in all children receiving thiopentone compared with 20 (66%) of those receiving propofol.
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The immunological mechanisms involved in Graves' ophthalmopathy are not known. To explore the pathophysiology of this disorder, we used an enzyme-linked immunosorbent assay to detect antibodies that bound to the 100,000 X g sediment fraction of porcine eye muscle. Serum from patients with Graves' ophthalmopathy had enhanced immunoglobulin binding to porcine eye muscle compared to serum from control subjects (P less than 0.0001); however, several individual normal serum samples also had elevated binding activity. Incubation of serum from some Graves' patients with skeletal muscle or liver tissue resulted in reduction in immunoglobulin binding to porcine eye muscle. Thyroglobulin and TSH reduced binding only at high concentrations. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed some obvious differences in protein bands between porcine eye muscle and skeletal muscle. Serum from many normal subjects and patients with autoimmune thyroid disease formed bands with skeletal muscle protein fractions on immunoblotting, and no specific bands were found using serum from Graves' ophthalmopathy patients. Immunoblots of Graves' patients' serum after reaction with either porcine skeletal or eye muscle showed no reactivity with thyroglobulin (200K and 320K) or thyroid microsomal antigen (105K). Instead, immunoblots of eye muscle and serum from Graves' patients, with or without eye disease, showed two bands at 64K and 73K, which were shared by serum from normal subjects. In addition, several unique eye muscle determinants were detected in serum from 6 of 13 Graves' disease patients analyzed. These unique bands usually had mol wt of less than 50K, and 5 of the 6 patients whose serum reacted with these determinants had significant ophthalmopathy. Our findings support the presence of potential antigenic differences between eye muscle and skeletal muscle accounting for the immunological specificity of eye muscle as a target in Graves' ophthalmopathy.
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We studied 30 diabetic pregnant women to compare serum fructosamine concentrations at different stages of gestation with fetal growth (as determined by ultrasonography) and with birth weight. Serum fructosamine levels in mothers of macrosomic infants were significantly higher (P less than .05) during the first trimester of pregnancy as compared with mothers of normal birth weight infants. Moreover, first-trimester fructosamine concentrations correlated significantly with birth weight (r = 0.68, P less than .001) and with ultrasound measurements of fetal abdominal circumference and femur length. The fetus destined to be macrosomic had an enlarged abdomen in the second trimester, often before 20 weeks' gestation. We conclude that maternal diabetic control during early gestation has an important influence on fetal growth and contributes to the development of fetal macrosomia.