Biomedical subjects
Publications and source records attributed to A Green.
Sweat tests were carried out on 14 patients with cystic fibrosis and 14 controls when on no antibiotics and when taking oral flucloxacillin. No significant differences in results were obtained for either group whether on or off antibiotics. Oral flucloxacillin does not affect sweat electrolytes and is not a contraindication to sweat testing.
The effect of a cloned allospecific human Th cell, termed 86, on the in vitro generation of altered self-reactive cytolytic T lymphocytes (CTL) was investigated. Utilizing the induction of hapten altered self-reactive CTL as a model for virus or tumor-specific cell-mediated immunity, we determined that the presence of small numbers of clone 86 cells markedly amplified the generation of hapten altered self-reactive CTL. The killer cells induced belong to the CD4-, CD8+ subset, are specific for the hapten-modified autologous stimulator cells present in culture, and are MHC class I restricted. The CTL induced under these culture conditions are readily expanded in the presence of IL-2 with maintenance of efficient and specific altered self-killing. Of interest, clone 86 cells preferentially enhance the growth of CD8+ T cells and selectively amplify altered self-cytolysis but not NK cell activity. Although in vitro clone 86 cells mediate help for CTL generation via the production of lymphokines (IL-4 but little IL-2), one can envision immunotherapeutic strategies for human disease that involve the adoptive transfer of Th cells functionally analogous to clone 86.
We have, in this paper, highlighted some of the common problems in amino acid analysis in our experience and listed the possible causes for increases in specific amino acids in urine--together with guidance on appropriate follow-up investigations.
Hyperammonaemia is associated with a high morbidity and mortality. It is important to diagnose as it is often treatable and perhaps, most importantly, may be genetically determined. Measurement of plasma ammonia is rarely necessary in adult medicine. In paediatrics, and particularly in the neonatal period, it is an important investigation in the diagnosis and often in the subsequent management of several inherited metabolic disorders. Patients with these disorders, particularly neonates, will deteriorate over a period of hours and investigation cannot wait. In these situations a plasma ammonia together with other investigations for metabolic disorders must be available urgently and are sometimes necessary out of normal laboratory hours. Interpretation must take into account the age and maturity of the child as well as the clinical state and results of other investigations. If treatment is initiated, frequent monitoring of plasma ammonia may be required. Plasma ammonia can be reliably and conveniently measured using a specific ion-selective electrode system or an automated enzyme method. Screening using a microdiffusion method is not a satisfactory alternative to a quantitative assay. Plasma ammonia is no longer solely the province of the specialised paediatric laboratory, but should be part of the repertoire of every laboratory supporting neonatal or paediatric units. The threshold for accepting requests should be lower than at present if we are to prevent misdiagnoses.
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The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.
The excretion of urinary iodine was studied in a representative population sample from the county of Funen, Denmark, comprising 505 persons between 25-44 years of age, stratified according to geography, age, and sex. Urine samples were collected for 5 h during late afternoon and early evening. The 24-h iodine excretion was estimated on the basis of iodine and creatinine determinations using correlation equations determined in a pilot study of 50 men and women. The iodine excretion was significantly higher in men: 89 micrograms/24 h (median) than in women: 76 micrograms/24 h; the whole population: 85 micrograms/24 h. No significant differences were observed among the age groups studied. The iodine excretion was significantly higher in people living on small islands: 98 micrograms/24 h (median) compared with 84 micrograms/24 h in urban regions and 78 micrograms/24 h in rural districts. Median iodine excretion per gram of creatinine was 58.8 micrograms for the whole sample. The iodine excretion for men was 77% higher than reported in an earlier investigation performed in Funen, 1969, but still lower than internationally recommended (WHO).
We report a 31-yr-old nondiabetic male patient with acanthosis nigricans whose hyperinsulinemia and insulin resistance could not be explained by anti-receptor antibodies or by an intrinsic defect of insulin binding to his cells. An acid-alcohol extract of the patient's serum contained a factor that inhibited insulin-stimulated glucose transport in rat adipocytes. Low levels of the factor could be detected in 9 of 13 unselected patients with non-insulin-dependent diabetes. The factor was heat stable and resistant to treatment with acid, base, and various lytic enzymes. It eluted from a Bio-Gel P-2 column with an apparent molecular weight of 300. The factor also inhibited stimulation of glucose transport in adipocytes by the insulin mimickers hydrogen peroxide and sodium vanadate. In vitro incubation of rat soleus muscles in the presence of the factor resulted in inhibition of insulin-stimulated glucose transport. The factor enhanced 125I-labeled insulin binding in both adipocytes and muscle. A preparation of insulin receptors obtained from muscles incubated with serum factor showed increased binding of 125I-insulin to the alpha-subunit of the insulin receptor. Autophosphorylation of the beta-subunit and phosphorylation of exogenous substrate were increased in the receptor preparation obtained from muscles that had been incubated with serum factor. However, the increase in kinase activity was approximately the same as the increase in binding activity. No difference in kinase activity was observed when assayed under conditions in which 125I-insulin binding activity had been equalized.(ABSTRACT TRUNCATED AT 250 WORDS)
Measurement of phenylalanine in plasma is required for the diagnosis and subsequent dietary management of phenylketonuria (PKU). We have developed an isocratic high-performance liquid-chromatographic (HPLC) method, with ultraviolet detection. For this measurement 10 microL of plasma is needed, and the complete analysis can be done in less than 15 min. Interbatch coefficients of variation for human plasma samples (phenylalanine 136-1541 mumol/L) ranged between 2.2% and 4.4%. The method has a wide linear range (10-3500 mumol/L), and results (y) correlated well with those (x) of an ion-exchange chromatographic method (r = 0.996; y = 1.014 x - 11.9; n = 64, range 22-1823 mumol/L). Only standard HPLC equipment is needed and no specialized sample preparation or detection system is required. The procedure has proved robust and reliable in regular routine use.
We prospectively examined the incidence of coronary heart disease in relation to cigarette smoking in a cohort of 119,404 female nurses who were 30 to 55 years of age in 1976 and were free of diagnosed coronary disease. During six years of follow-up, 65 of the women died of fatal coronary heart disease and 242 had a nonfatal myocardial infarction. The number of cigarettes smoked per day was positively associated with the risk of fatal coronary heart disease (relative risk = 5.5 for greater than or equal to 25 cigarettes per day), nonfatal myocardial infarction (relative risk = 5.8), and angina pectoris (relative risk = 2.6). Even smoking 1 to 4 or 5 to 14 cigarettes per day was associated with a twofold to three-fold increase in the risk of fatal coronary heart disease or nonfatal infarction. Overall, cigarette smoking accounted for approximately half these events. The attributable (absolute excess) risk of coronary heart disease due to current smoking was highest among women who were already at increased risk because of older age, a parental history of myocardial infarction, a higher relative weight, hypertension, hypercholesterolemia, or diabetes. In contrast, former smokers had little, if any, increase in risk. These prospective data emphasize the importance of cigarette smoking as a determinant of coronary heart disease in women, as well as the markedly increased hazards associated with this habit in combination with other risk factors for this disease.
Adenosine, via interaction with A1 adenosine receptors, increases insulin sensitivity and inhibits lipolysis in adipocytes. To investigate regulation of this system, adipocytes were incubated for up to 72 h with the nonmetabolizable adenosine receptor agonist, N6-phenylisopropyl adenosine (PIA). Adenosine receptors were measured by the binding of 125I-hydroxyphenylisopropyl adenosine to membranes. PIA down-regulated adenosine receptors, decreasing the number of binding sites with no change in affinity. Adipocytes were incubated for 48 h without or with 100 nM PIA to down-regulate the A1 receptors by approximately 60%. The cells were washed, and lipolysis and glucose transport were assessed. The ability of PIA to inhibit lipolysis was markedly attenuated in the down-regulated cells. Furthermore, the EC50 of insulin was increased approximately 3-fold in the PIA-treated cells. 125I-Insulin binding to the PIA-treated cells was unchanged, demonstrating that the decreased insulin sensitivity is not due to decreased insulin receptor binding. Pertussis toxin catalyzed ADP-ribosylation of a 41-kDa protein thought to be the alpha-subunit of Gi. This 41-kDa protein was decreased in membranes from cells treated with PIA, with a maximal 50% loss. This suggests that Gi is down-regulated and that loss of both the A1 adenosine receptor and Gi are involved in the metabolic changes observed after PIA treatment.
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HLA typing for the A and B loci was carried out in conjunction with measurements of iron status on 38 of the first-degree relatives of 8 patients suffering from idiopathic haemochromatosis (IHC). Seven of the 8 probands had the A3 allele, 2 in the homozygous form. Seven had the B7 allele and in 5 it was present with the A3 allele on the same chromosome. Six family members were diagnosed as homozygous for the HLA-linked iron-loading gene on the basis of genotype assessment, while 27 were assessed as being heterozygous. Five of the 6 homozygous subjects had developed significant iron overload. In contrast, disturbances of iron metabolism in the heterozygotes were mild and present in only 33%. Pseudodominant inheritance of IHC was noted in one family, presumably as the result of a homozygous/heterozygous mating. A pilot epidemiological survey was carried out on 222 Afrikaans-speaking men in an attempt to find affected individuals using the serum ferritin concentration as the screening test. One homozygous subject was identified (genotype A3, B7/A3, B7) and further family studies confirmed the presence of the HLA-linked iron-loading gene. These preliminary results suggest a disease frequency of about 4-5/1,000 in the Afrikaner population.
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