Treatment of acute idiopathic thrombocytopenic purpura.
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Biomedical subjects
Publications and source records attributed to C Turner.
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Pitch-intensity functions and psychophysical tuning curves (PTC's) were measured in ten listeners with sensorineural impairments of presumed cochlear origin. Masking patterns, frequency jnd's, diplacusis measurements, and octave adjustments were also obtained for selected conditions in selected listeners. The results showed a tendency for increased frequency jnd's and increased pitch-matching variability in frequency regions where frequency resolution, as determined by PTC Q10 estimates, was degraded. The results also showed exaggerated pitch-level effects, both in regions where frequency resolution was degraded and, in many cases, in regions where thresholds and frequency resolution were apparently normal. The usual manifestation of exaggerated pitch-level effect was an abnormally large negative pitch shift with increasing level, particularly at low frequencies. The limited data from diplacusis measurements and octave adjustments suggest that the exaggerated negative pitch shifts are the consequence of a large increase in pitch at low stimulus levels which "recruits" at higher levels. These results are difficult to explain with simple tonotopic models, or presently formulated temporal models, of pure-tone pitch encoding.
Six children with chronic renal failure were treated with dietary protein restriction and essential amino acid and keto acid supplements for 6 months. Dietary protein and phosphate intake decreased, dietary calcium increased, and dietary carbohydrate and energy did not change. Plasma urea and urea to creatinine ratio decreased significantly during treatment. Glucose metabolism was studied before and after 6 months of treatment using the hyperglycemic clamp technique. Fasting hyperglycemia, glucose intolerance, and insulin resistance improved during treatment, while fasting insulin and insulin levels during hyperglycemia did not change. These metabolic changes were not related to hyperparathyroidism and were probably due to reduction in nitrogen toxicity.
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We studied the serum lipid profiles of 29 children, 3.9-17.9 years of age who were 0.6-7.6 years after renal transplantation (Tx). Twenty normoglycemic and non-proteinuric children had a well functioning allograft and 5 children had reduced renal function. Both groups were at least 7 months on alternate day corticosteroid (ADCS) therapy. Four additional patients had good renal function but were only 2.3 +/- 0.5 months on an ADCS regimen. Fifteen normal children served as controls. The levels of serum triglycerides (STG) and total cholesterol (CHOL) were elevated and high-density lipoprotein CHOL (HDL-CHOL) were low in all patients compared to control subjects (p less than 0.01). Their cardiovascular risk factor (CHOL/HDL-CHOL) was increased. The lipid abnormalities were most prominent in Tx patients with reduced graft function. These data show that treatment with ADCS does not prevent post-Tx hyperlipidemia. More insight is needed into the mechanisms responsible for the hyperlipidemia after Tx in order to reduce possible future morbidity (and mortality) from premature cardiovascular disease in this group of young, high-risk patients.
Cyanogen bromide (CNBr) cleavage of total rat liver histone H1 generates a C-terminal peptide which originates from a methionine-containing subfraction. This subfraction comprises approx. 20% of the whole rat liver H1 population, resembles calf thymus CTL-1 in size but contains methionine and histidine, higher proportions of serine and less alanine and proline. Edman degradation established the N-terminal sequence of the CNBr peptide as Arg-Arg-Lys-Ala-Ser-Gly-Pro-Pro-Val-Glu. By alignment with calf thymus CTL-1, methionine was identified as residue 30 replacing alanine in a non-conservative replacement. Residue 40 is deleted but sequence homology near the double proline sequence in the G-domain is retained. The CNBr peptide is estimated at 177-181 residues and comprises the complete G- and C-domain and two arginines from the basic cluster in the N-domain. Removal from H1 of all but two residues of the N-domain does not abolish secondary and tertiary folding. This GC-peptide opens new approaches to the study of the function of H1 in chromatin.
Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure.
A semi-automatic system incorporating an ultra-sensitive interference refractometer coupled to a dual-column gel permeation apparatus has been devised for measurement of the molecular size distribution of dextrans in small samples of serum and urine. The system was calibrated with seventeen defined dextran fractions with a range of 1200-250,000 weight average molecular weight (Mw). Urine samples were prepared for analysis by passage through small ion-exchange columns; serum was pretreated by precipitation with trichloroacetic acid and centrifuged before the ion-exchange treatment. Internal standard (dextran, 2 X 10(6) Mw) was added to each sample before pretreatment. Data were obtained in a form suitable for computerised analysis.
Most dissociated airway epithelial cells in culture express few of their in vivo functions and only to a limited degree. In this report, we demonstrate that hamster tracheal epithelial (HTE) cells cultured on a collagen gel substratum in a serum-free hormone-supplemented medium differentiate to cilia-beating and mucus-secreting cell types. The medium is Ham's F-12 supplemented with insulin, epidermal growth factor, transferrin, hydrocortisone, cholera toxin, bovine hypothalamus extract, and vitamin A. Under these culture conditions, HTE cells exhibit a growth rate of 24 h/population doubling and reach confluency, at a density of 2-5 X 10(4) cells/cm2, within 2 weeks. Both the collagen gel substratum and vitamin A of this culture system are important to the growth and differentiation of HTE cells in vitro. Evidence of HTE cell differentiation has been obtained at both the ultrastructural and the histochemical levels. In addition, a variety of biochemical studies (gel filtration, ion exchange column chromatography, enzyme digestion, nitrous acid treatment, and composition analysis) indicate the production of mucin-like glycoprotein in the HTE cultures. The levels of mucin-like glycoprotein were found to closely correlate with the histochemically quantitated levels of the mucous cell type. Kinetic studies demonstrate that HTE cells rapidly lose their differentiated features during the attachment stage of primary culture but redifferentiation occurs after the cultures reach confluency. The ability of HTE cells to grow and differentiate in this serum-free culture system in the absence of other cell types should greatly facilitate the study of mucociliary functions in vitro.
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In an open chested dog model utilizing dual isotope techniques (125I heptadecanoic acid and 9, 10 3H palmitic acid), sequential myocardial biopsies were performed to: validate the scintigraphic background subtraction technique for the iodo fatty acid, compare the myocardial activity time course for the fatty acids and by TLC methods determine the chemical form of the myocardial activity and to study the influence of free iodide on the overall time-activity pattern. The findings supported the method of background subtraction and demonstrated a similar activity-time course for the two fatty acids. In spite of this, approximately 30% of the myocardial activity (125I) was in the form of free iodide which suggested that the rate of diffusion of iodide may be an important kinetic element in the system. Some differences in the lipid form of the radioactivity (3H, 125I) were noted.
We studied glucose metabolism in a group of adolescents and young adults with uremia using the hyperglycemic clamp technique. In eight adolescent patients, the glucose metabolic rate correlated negatively with PTH levels and positively with the glomerular filtration rate. Six patients, one adolescent and five adults on regular hemodialysis with severe hyperparathyroidism, had low glucose metabolic rates and reduced insulin sensitivity compared to normal subjects. After parathyroidectomy, the glucose metabolic rate improved by 47%; plasma insulin concentrations during hyperglycemia increased by 37%, and insulin sensitivity did not change significantly. Thus, correction of hyperparathyroidism was associated with normalization of glucose metabolic rates and increased insulin secretion, but insulin resistance did not change.
The specific airway conductance response of six normal subjects to increasing doses of inhaled histamine was studied on two occasions. On each occasion either epinephrine (0.025 micrograms/kg/min) or saline was infused intravenously during the histamine challenge. This dose of epinephrine, when it was administered to seated normal subjects, produces plasma levels similar to those found at the end of strenuous exercise. Epinephrine caused a significant elevation in the concentration of histamine required to cause a 35% fall in specific airway conductance (PC35), although this was in part caused by a small airway dilator effect. The mean (+/-SD) PC35 rose from 21 mg/ml (+/-6) during saline infusion to 58 mg/ml (+/-27) during epinephrine infusion, p less than 0.05. Levels of circulating epinephrine, similar to those found during exercise in normal subjects, appear to be capable of protecting against bronchoconstrictor stimuli.
By studying six normal subjects during graduated treadmill exercise, we have confirmed that there is very little rise in venous plasma adrenaline levels during mild or moderate exercise. During a second study, adrenaline was infused intravenously in six resting subjects at a rate of 0.025 micrograms min-1 kg-1. This elevated the basal plasma adrenaline level from 0.28 +/- 0.04 nmol/l to 0.92 +/- 0.16, 1.16 +/- 0.20 and 1.28 +/- 0.19 nmol/l at 3, 5 and 7 min after the start of the infusion. The same adrenaline infusion was repeated in the same subjects 7 min after they started moderate exercise at a constant rate on a static exercise bicycle. Just before the start of the infusion, 7 min after the onset of exercise, plasma adrenaline had risen to 0.36 +/- 0.07 nmol/l. This rose to 1.86 +/- 0.30, 1.98 +/- 0.26 and 2.19 +/- 0.29 nmol/l at 3, 5 and 7 min after the start of this second infusion. Five minutes after the end of the infusion, while the subjects were still exercising, the mean level was 0.56 +/- 0.04 nmol/l. The venous plasma level of adrenaline is the result of a balance between the secretion of adrenaline by the adrenal medulla and the clearance of adrenaline from plasma. Our results suggest that the lack of any significant rise in plasma adrenaline during moderate exercise does not result from an accelerated clearance of adrenaline by exercising tissue. The clearance rate of adrenaline from plasma is reduced during exercise. There is no significant increase in secretion by the adrenal medulla in response to the stimulus of mild or moderate exercise.
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The 1H-n.m.r. spectra of human somatotropin (growth hormone) show perturbed peaks from individual aromatic and aliphatic apolar residues, characteristic of a specifically folded globular structure. The imidazole C-2-H resonances of the histidine residues (at positions 18, 21 and 151 in the somatotropin sequence) were individually resolved, and their titration behaviour in the pH range 1.2-11.5 was investigated. The imidazole C-2-H resonance of histidine-151 is assigned, by comparison of its titration behaviour in human somatotropin and desamido-somatotropin (Asn-152 leads to Asp-152). The C-2-H resonances of all three histidine residues are assigned, by comparison of their relative deuterium-exchange rates (determined by n.m.r.) and the relative tritium-exchange rates of the histidine residues (determined by tryptic digestion of tritiated human somatotropin and reversed-phase high-pressure liquid-chromatographic separation of the histidine-containing tryptic peptides). There is evidence that histidine-18 forms an ion-pair bond with a glutamic acid or aspartic acid residue. The globular structure does not appear to change from pH3 to 11.5, though there is evidence for an unfolding of a region of the structure (involving histidine-21 and a tyrosine residue) below pH3.
The chromosomal proteins HMG1 and 2 have been prepared by salt extraction and phosphocellulose chromatography at neutral pH (Isackson, P.J., Debold, W.A. and Reeck, G.R. (1980) FEBS Lett. 119, 337-342) to minimize protein denaturation. The structures of these phosphocellulose-prepared high mobility group proteins have been compared with those of high mobility group proteins using the previously described acid-extraction conditions which fully denature the proteins. When compared in the same solvent conditions the acid-extracted proteins did not refold to give the same level of alpha-helical and tertiary folded structures as the phosphocellulose-prepared proteins, suggesting that acid treatment can cause some irreversible damage to the proteins. This finding was supported by changes in the structure observed when phosphocellulose-prepared HMG1 was neutralized after exposure to acid. Gel filtration studies reveal no differences in the size of the high mobility group proteins, phosphocellulose-prepared and acid-extracted proteins both being largely monomeric in solution. Little difference was detected in the DNA-binding properties of the two types of protein, nor was there any difference in the oxidation state of the cysteines. However, isoelectric focusing analysis revealed differences in the subfractions of HMG2 prepared by the two methods.