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Biomedical subjects

C J Taylor

Publications and source records attributed to C J Taylor.

At least 163 records · Page 9Linked to original sources

A positive B cell crossmatch due to IgG anti-HLA-DQ antibody present at the time of transplantation in a successful renal allograft.

The role of a positive B cell crossmatch in renal transplantation is uncertain, partly because of the difficulty in determining the true specificity of the various antibodies that may cause a positive crossmatch. We have used monoclonal antibodies against HLA class I, HLA-DR and HLA-DQ antigens to inhibit cytotoxicity of sera from renal patients, in order to define the specificity of a positive B cell crossmatch. We have used reduction with dithiothreitol (DTT) to identify the immunoglobulin class. These methods were used to identify the specificity and immunoglobulin class of the antibody causing a positive B cell crossmatch in a highly sensitised patient. The results show that the antibody was IgG anti HLA-DQ and the graft was functioning 1 year after transplantation. Immunoperoxidase techniques demonstrated a normal expression of HLA-DQ antigen in biopsies of the transplanted kidney. The successful outcome of the transplant raises questions about the role of anti-HLA class II antibodies in renal transplantation.

B-Lymphocytes↗

A kwashiorkor-like syndrome in a Caucasian with enteropathy.

A Caucasian child with congenital heart disease (CHD) presented at the age of 19 months with a kwashiorkor-like syndrome. Jejunal biopsy showed sub-total villus atrophy. The clinical picture of repeated infection causing growth faltering followed by oedema, hair and skin changes, resembled the response to infection of many nutritionally stressed children in the tropical world. The exact aetiology of kwashiorkor and the diagnostic specificity of its clinical features remain in doubt, as does precise definition. This case highlights the problems of diagnosing a condition which is essentially the end point of a combination of nutritional and environmental stresses.

Celiac Disease↗

Ultrastructural and biochemical changes in human jejunal mucosa associated with enteropathogenic Escherichia coli (0111) infection.

A case of prolonged diarrhoea following Escherichia coli 0111 gastroenteritis is reported. Electron microscopy of the jejunal biopsy revealed effacement of the brush border and attachment of bacteria by pedestal formation. Specific activities of brush border enzymes showed marked depression of disaccharidases, zinc-resistant alpha-glucosidase, and alkaline phosphatase. In contrast, marker enzymes for basolateral membranes and endoplasmic reticulum were unaffected. The biochemical changes support the pathogenic mechanism suggested by ultrastructural studies previously reported.

Biopsy↗

Immunoglobulin class and specificity of antibodies causing positive T cell crossmatches. Relationship to renal transplant outcome.

A group of 42 renal transplants performed in the presence of a T-cell-positive crossmatch were analyzed to determine the class and specificity of the donor-reactive cytotoxic antibodies. Dithiothreitol (DTT) was used to reduce IgM antibodies and a monoclonal antibody directed at a monomorphic determinant present on all HLA class I antigens (PA2.6) was used to inhibit cytotoxicity of anti-HLA class I antibodies. Sera from 26 of the positive crossmatches were considered to be autoreactive, and the positive crossmatch proved to be due to IgM and not directed at HLA class I in each case. One year graft survival was 100% in the 5 living-related and 60% in the 21 cadaver donor transplants, of which 10 were regrafts. Of the 42 positive crossmatches, 16 were not due to autoantibody. One was positive in the current serum taken at the time of transplantation, and this graft was rejected hyperacutely, while 15 were positive with peak but not current serum samples. Of the positive crossmatches, 12 were inhibited by PA2.6 demonstrating that they were directed at HLA class I antigens. PA2.6 inhibition could not be shown in 3 and in 1 DTT reduction was technically unsatisfactory. While 4 of the 7 positive crossmatches due to IgM antibodies were successful, the 7 transplants performed with positive crossmatches due to IgG antibodies all failed. DTT reduction and inhibition of cytotoxicity by PA2.6 helps to define positive crossmatches with donor T cells that are not associated with graft failure. Transplantation in the presence of a peak positive T cell crossmatch due to an anti-HLA antibody might only be successful if the antibody in the peak serum is of the IgM class.

Antibodies, Monoclonal↗

Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle.

The effects of a synthetic atrial peptide (atriopeptin II; AP II) on the agonist-induced intracellular Ca2+ release was examined in the isolated rabbit aorta. The agonist-induced phasic contraction in a Ca2+-free physiological salt solution containing 2 mM ethyleneglycol-bis(beta-aminoethyl-ether)-N,N'-tetraacetic acid (EGTA-PSS) was used as an indicator of the intracellular Ca2+ release. The addition of AP II (10(-9)-10(-7) M) for 15 min to the tissue during the EGTA-PSS exposure caused a dose-dependent inhibition of norepinephrine (NE; 10(-6) M)-induced phasic contraction. The half-maximal inhibiting concentration of AP II was 3 X 10(-9) M, with 10(-7) M AP II causing 91% inhibition. This was confirmed by studying the inhibitory effect of AP II (10(-7) M) on NE-stimulated 45Ca efflux. Furthermore, the internal Ca2+ release by histamine (10(-5) M) and caffeine (25 mM), both of which share this internal Ca2+ pool with NE, was also inhibited by AP II. Thus AP II appears to be a potent inhibitor of the intracellular Ca2+ release that is utilized by various agonists for the activation of vascular smooth muscle. This may be an important mechanism by which AP II produces relaxation of blood vessels.

Animals↗

Inhibitory effects of a synthetic atrial peptide on contractions and 45Ca fluxes in vascular smooth muscle.

The mechanism of a synthetic atrial peptide (APII)-induced inhibition of smooth muscle contractility was investigated by studying its effects on tension development and 45Ca fluxes in isolated rabbit aorta. APII (10(-9) to 10(-7) M) produced a dose-dependent relaxation of contractions produced by alpha adrenoceptor activation with norepinephrine (NE; 10(-6) M). APII was a potent relaxant of NE contraction with an IC50 = 1.1 X 10(-8) M, with 10(-7) M APII causing a 97% relaxation. APII also produced a dose-dependent inhibition of NE contraction when added to the resting muscle before the exposure to NE. The relaxing effects of APII were found to be endothelium independent. In contrast, APII was only marginally effective in relaxing high-K+ contraction, with 10(-7) M APII causing only 17% relaxation. Furthermore, when a NE contraction was obtained on top of a high-K+ contraction, APII was still capable of relaxing the NE component. APII was similarly more effective in inhibiting NE-stimulated 45Ca influx than high-K+-stimulated 45Ca influx, indicating selective action of APII on the receptor-operated Ca++ channels. This was in contrast to D600, a well known Ca++ antagonist, which had a more selective inhibitory effect on the potential-operated Ca++ channels. The data presented indicate that APII is a potent relaxant of contractions produced by receptor-agonists involving 45Ca influx through receptor-operated Ca++ channels. APII may also prove to be a very useful tool to further distinguish and define receptor-operated Ca++ channels and potential-operated Ca++ channels in vascular smooth muscle.

Acetylcholine↗

Ulcerative colitis and HLA phenotype.

The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.

Adolescent↗

HLA-DR typing in coeliac disease: evidence for genetic heterogeneity.

Sixty nine propositi from a family study of coeliac disease were typed for HLA-DR antigens. Sixty three (91%) were found to carry the antigen DR3, which was a significantly greater proportion (p = 9.6 X 10(-24] than among the 168 controls (26%). Concurrently 42 children with the disease were DR typed. Not only was the frequency of DR3 significantly increased in these patients (86% versus 26% in controls; p = 3.1 X 10(-12] but so also was the frequency of DR7 (patients 60%, controls 29%; p = 5.8 X 10(-4]. When those propositi whose coeliac disease presented before the age of 20 were combined with the childhood coeliac group and a comparison made between these patients and the remainder of the propositi, all of whom presented when they were older than 20, the childhood onset group had a significant excess of DR7 (p = 2.2 X 10(-3] and a significant deficiency of DR2 (p = 3.5 X 10(-3]. These findings indicate that childhood coeliac disease and adult coeliac disease are genetically heterogeneous.

Adult↗

A conformationally constrained vasopressin analog with antidiuretic antagonistic activity.

Application of information derived from a three-dimensional model of vasopressin bound to its antidiuretic receptor resulted in the design and synthesis of a bicyclic vasopressin analog, [5,8-cyclo(1-beta-mercaptopropionic acid,2-phenylalanine,5-aspartic acid,8-lysine)]vasopressin. The analog acts as an antagonist of the antidiuretic activity of vasopressin.

Animals↗

The effect of treatment on zinc, copper and calcium status in children with phenylketonuria.

The trace element status of 25 children receiving a low phenylalanine diet for a treatment of phenylketonuria was studied using hair and serum samples. Hair trace element and calcium concentrations were assayed using X-ray microanalysis and compared with samples from sibling controls. Plasma, zinc and copper levels were compared with unselected hospital attenders. PKU patients were found to have significantly lower hair zinc (P less than 0.001) and calcium (P less than 0.01) concentrations and significantly hair copper (P less than 0.001) concentrations compared with controls. Plasma zinc levels were below the lower limit of normal (9.6 mumol l-1) in 8 of 19 patients (42%) in whom it was measured. The relative zinc deficiency in PKU patients may result from a competitive inhibition of absorption by copper or other metals supplemented in the diet.

Adolescent↗

Effects of the highly selective kappa opioid, U-50, 488, on renal function in the anesthetized dog.

Intravenous administration of U-50,488 (a chemically novel and highly selective kappa agonist) resulted in dose-dependent increases in urine formation in anesthetized dogs. The increase in urine formation was not accompanied by an increase in sodium or potassium excretion; thus, U-50,488 behaved like a water diuretic. In addition, a dose-dependent fall in blood pressure was noted after U-50,488 administration. Despite the effect on blood pressure, no changes in renal plasma flow (p-aminohippurate clearance) or glomerular filtration rate (inulin clearance) were detected at any dose tested. Apparently, the diuresis was primarily due to tubular effects and not to changes in renal hemodynamics. Intravenous infusion of antidiuretic hormone (2 pmol/min/kg) abolished completely the diuretic response to U-50,488 (5 mg/kg). This implied that the diuresis was mediated by an effect of the drug on antidiuretic hormone.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Myoglobin concentration, creatine kinase activity, and creatine kinase B subunit concentrations in serum during thyroid disease.

Changes in values for myoglobin, total creatine kinase (EC 2.7.3.2), and creatine kinase B-subunit in the serum of patients with thyroid disease are compared with values for these during the 24-h after myocardial infarction. Concentrations of all three of these muscle-derived proteins were significantly higher than normal in patients with primary hypothyroidism, and declined with treatment. Values for total creatine kinase activity were below-normal in hyperthyroid patients, but increased after treatment. Values for total creatine kinase and, to a lesser extent, myoglobin in hypothyroidism extend into the range of values observed after myocardial infarction. The mechanism of the changes in these analytes in hypothyroidism may be related to increased leakage from skeletal-muscle cells or diminished clearance from the circulation, or both.

Creatine Kinase↗

Anthropometric standards for term neonates.

32 anthropometric measurements have been carried out (within 48 h of birth) on 106 full-term normal neonates. Trunk and limb parameters are considered and the results presented as mean values with standard deviations. Comparison with previously published standards, where available, showed good agreement. Both sides of the body were measured but no significant difference was found overall between values for left and right sides of the body. The effect of gender on each measurement was also considered with females having significantly smaller head circumferences and head lengths and larger upper leg lengths.

Anthropometry↗

Non-accidental paracetamol poisoning in an eleven month-old child.

1 Although accidental poisoning of children with drugs and chemicals is a common precipitant for admission to hospital, the possibility of deliberate poisoning as an extension of 'the battered baby syndrome' is rarely considered. 2 Most children admitted following accidental ingestions require little active management other than induction of emesis. Report of relatively large overdoses in infancy are rare, and protocols for management of such cases largely untried. This case report demonstrates the successful application of a current treatment regimen to an infant who had ingested a substantial quantity of paracetamol.

Acetaminophen↗

Inhibition of ADH-stimulated water flow by stable prostaglandin endoperoxide analogues.

The synthetic prostaglandin endoperoxide analogues 15-hydroxy-9,11-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-I) and 15-hydroxy-11,9-(epoxymethano)prosta-5,13-dien-1-oic acid (EPA-II) inhibited ADH-induced water flow in the isolated urinary bladder of the toad. In certain other biologic systems, EPA-I appeared to possess "thromboxane-like" activity. Thromboxanes, therefore, as well as the classical E prostaglandins may be modulators of the ADH response. To further characterize the effect of EPA-I on ADH, interaction studies were conducted with a related endoperoxide analogue found to be devoid of anti-ADH activity, 9,11-(epoxymethano)prostan-1-oic acid (EPA-III), and a prostanoid found to be a PGE antagonist in isolated toad bladder, 7-oxa-13-prostynoic acid. EPA-III reversed the anti-ADH activity of EPA-I but not that of PGE2. In contrast, 7-oxa-13-prostynoic acid reversed the anti-ADH activity of PGE2 but not that of an equieffective concentration of EPA-I. These findings suggest that the anti-ADH activity of EPA-I, and by inference thromboxane A2, may be mediated via a different receptor and/or pathway than that of the E prostaglandins.

Animals↗