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The cosecretion of pancreatic lipase and colipase are important in normal fat digestion. As adsorption of phosphatidylcholine to the lipid substrate interferes with lipase activity, hydrolysis to lysophosphatidylcholine with subsequent desorption is also essential for fat digestion. There are some data regarding the secretion of pancreatic phospholipases in normal adults but none in children or patients with pancreatic disease. In the present study, we aimed a) to develop an accurate fast assay method to measure phospholipase A(2) and b) to determine the secretion rate of pancreatic phospholipase A(2) and whether it is cosecreted with lipase and colipase in children with exocrine pancreatic dysfunction. Nine male patients aged 0.5 to 16 y (seven with cystic fibrosis, two with malabsorption) underwent pancreatic stimulation tests. Their colipase and lipase secretion rates were measured by titrimetric methods and phospholipase A(2) and A(1) by phosphorus magnetic resonance spectroscopy ((31)P NMR). It was found that the phospholipases, colipase, and lipase were absent in the two patients with pancreatic insufficiency. In patients with normal absorption, there were marked inter-and intrasubject variations of lipase, colipase, and phospholipase secretion rates that were consistent with the degree of exocrine pancreatic dysfunction. However, in the three 20-min stimulation periods of the pancreatic function test, pancreatic phospholipase is cosecreted with lipase and colipase, and average colipase and phospholipase A(2) secretion rates follow a similar or parallel pattern. These findings are consistent with the important role of pancreatic phospholipases in intestinal phospholipid hydrolysis leading to the desorption of phospholipids from the lipid substrate and enhancing lipid hydrolysis and phospholipid absorption. 相似文献
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The incidence of transient hypogammaglobulinaemia of infancy (THI) detected in a major paediatric centre over a 10 year period was examined. A total of 2468 subjects less than 2 years of age had an IgG measurement taken between July 1979 and March 1990. Subjects with known immunodeficiencies were excluded. Fifteen patients were classified as having THI with an initial IgG level less than the fifth centile followed by a second measurement within the normal range. A further 24 patients were identified as having possible THI with a single low IgG concentration. There were 60,174 live births each year in Victoria in the years 1979-88. This gives an incidence of proved THI of 23 per 10(6) births, and including proved and probable THI an incidence of 61 per 10(6) live births. Of those patients with proved THI 12/15 had symptoms of either atopic disease or food allergy/intolerance and three had gastrointestinal symptoms without any evidence of atopic disease. At presentation 12/15 (80%) were IgA deficient and 9/15 had IgM concentrations less than the 20th centile for age. It is suggested that in view of the preponderance of atopic and food intolerant patients that subclinical protein loss from the bowel due to allergic inflammation may be a contributing factor to the development of THI in some patients. 相似文献
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Administration of a single oral dose of 2-(2-nitro-4-trifluoromethyl-benzoyl)-cyclohexane-1,3-dione (NTBC) to mice increases the concentration of tyrosine in the plasma and aqueous humour. The tyrosinaemia is both time and dose-dependent with a single dose of 30 micromol NTBC/kg (10 mg/kg) producing maximal concentrations of tyrosine in plasma of about 1200 nmol/ml and in aqueous humour of about 2200 nmol/ml at 16 h after dosing. Analysis of the key hepatic enzymes involved in tyrosine catabolism, following a single dose of 30 micromol NTBC/kg, showed that 4-hydroxyphenylpyruvate dioxygenase (HPPD) was markedly inhibited soon after dosing and that the activity recovered very slowly. In response to the tyrosinaemia, the activity of hepatic tyrosine aminotransferase (TAT) was induced about two-fold, while the activity of hepatic homogentisic acid oxidase (HGO) was reduced at 4 and 5 days after dosing. Daily oral administration of NTBC at doses up to 480 micromol NTBC/kg (160mg/kg/day) to mice produced a maximal tyrosinaemia of about 600-700nmol/ml plasma, showing some adaptation relative to a single dose. Unlike the rat, no treatment-related corneal lesions of the eye were seen at any dose levels up to 6 weeks. Administration of a single oral dose of [14C]-NTBC at 30 micromol/kg led to selective retention of radiolabel in the liver and to a lesser extent the kidneys. Our studies show that NTBC is a potent inhibitor of mouse liver HPPD, which following repeat exposure produces a marked and persistent tyrosinaemia, which does not result in ocular toxicity. 相似文献
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STOTT DJ; MCLELLAN AR; FINLAYSON J; CHU P; ALEXANDER WD 《QJM : monthly journal of the Association of Physicians》1991,78(1):77-84
The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (412)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism. 相似文献
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HLA class II genes were examined in patients with small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) using restriction fragment length polymorphism and allele specific oligonucleotide typing. Fifty-nine patients were studied, 34 with Wegener's granulomatosis and 25 with microscopic polyarteritis, and their results were compared with those from 1103 British Caucasoid controls. The frequency of HLA-DQw7 was significantly increased in patients with vasculitis (patients 53%; controls 27.8%, chi 2 17.8, Pc less than 0.0025, relative risk 2.9), and all the DQw7 bearing haplotypes commonly found in Caucasoid populations contributed to the increase. By contrast, the frequency of HLA-DR3 bearing haplotypes was decreased in the patients (patients 6.8%; controls 21.6%, chi 2 6.7, P less than 0.01). HLA specificities were similar in the groups of patients presenting with Wegener's granulomatosis and microscopic polyarteritis and with different types of ANCA assessed by indirect immunofluorescence. However, patients with the DQw7, DR4 haplotype were significantly more likely to have transiently positive tests for ANCA than patients with other DQw7 bearing haplotypes, whereas patients with DR2 bearing haplotypes were more likely to have persistently positive ANCA. These results show that HLA class II genes are associated with small vessel vasculitis and may influence the duration of the associated autoimmune response. 相似文献