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Biomedical subjects

C E Price

Publications and source records attributed to C E Price.

At least 19 recordsLinked to original sources

Partial cloning and sequencing of chick fibrillin-1 cDNA.

The recent identification of numerous matrix genes and gene products has allowed a detailed examination of their roles in development. Two of these extracellular matrix proteins, fibrillin-1 and fibrillin-2, are components of the elastin-associated microfibrils. Given what is known about the distribution of the fibrillins in normal tissues and the abnormalities that result when mutations occur, a basic hypothesis has emerged: fibrillin-1 is primarily responsible for load bearing and providing structural integrity, whereas fibrillin-2 may be a director of elastogenesis. Nevertheless, examination of phenotypes in disorders caused by mutations in fibrillin-1 or fibrillin-2 suggests some common functions. To better understand these similar and diverse roles, it would be helpful to examine these proteins during chick development. To accomplish this goal, it is first necessary to characterize the chick homologs of the known fibrillins. In this study, the partial chick FBN1 cDNA was identified by polymerase chain reaction-aided cloning as a first step toward elucidating these goals. Sequence analysis indicated that there is striking conservation between chick and mammalian fibrillin-1 at the DNA and protein levels. Antisense and sense riboprobes were synthesized and used in in situ hybridization in stage 14 chick embryos and high levels of FBN1 transcripts were observed in the heart.

Amino Acid Sequence↗

Biaryl acids: novel non-nucleoside inhibitors of HIV reverse transcriptase types 1 and 2.

A series of biaryl acids has been found to show micromolar inhibition of the HIV reverse transcriptase (RT) from types 1 and 2 with IC50S in the micromolar range. The series was discovered by consideration of the polymerase active site and sub-structure searching of the company compound collection. Synthesis of analogues to investigate the SAR is described. Two of these compounds have shown inhibition of HIV-2 RT only.

Anti-HIV Agents↗

Prenatal and presymptomatic diagnosis of the Marfan syndrome using fluorescence PCR and an automated sequencer.

The Marfan syndrome (MFS) is a heritable connective tissue disorder characterized by skeletal, ocular, and cardiovascular abnormalities. Defects in fibrillin, an elastin-associated microfibrillar protein, are now known to cause MFS. Since the discovery of fibrillin as the gene responsible for MFS, requests for prenatal and presymptomatic diagnosis have become common-place. Here we report the use of the polymerase chain reaction (PCR), using fluorescence labelled primers and an automated sequencer, to establish linkage data for 'molecular diagnosis'. The mistaken clinical diagnosis of MFS based on the appearance of a common cardiovascular manifestation, mitral valve prolapse, and a positive family history is also discussed.

Autoanalysis↗

Prospective study of the quality of life in patients assessed for liver transplantation: outcome in transplanted and not transplanted groups.

The quality of life in adult patients with chronic liver disease who were considered for transplantation was assessed prospectively over a 2 year period, for both those who did and did not subsequently receive transplants. The main outcome measures were the Nottingham Health Profile and survival. Of the 109 patients who completed an entry profile, 27 were transplanted, 71 not transplanted during the study period, and 11 rejected for transplant. Quality of life and severity of liver disease at entry was worse for the transplant group, whose survival at 15 months from entry was 81% compared with 78% for those not transplanted. Among transplant survivors there were marked improvements in quality of life, whilst amongst those not receiving transplants there was little change. In conclusion, liver transplantation was effective in improving quality of life in patients with chronic liver disease, but comparison between transplant and non-transplant patients is difficult because of differences between the groups.

Activities of Daily Living↗

Equity and medical practice variation: relationships between standardised discharge ratios in total and for selected conditions in English districts.

STUDY OBJECTIVE: The aim was to investigate relationships for residents of English district health authorities between rates of discharges from acute hospitals for all conditions and variations in discharge rates for eight common conditions (five surgical, three medical). DESIGN: Hospital Inpatient Enquiry data on discharges for 1984 were analysed. Standardised discharge ratios (ratios of actual to expected numbers of discharges x 100) were derived for selected conditions and all conditions; and correlation coefficients for these statistics were calculated. Districts were grouped into quintiles according to the value of the standardised discharge ratio, and systematic variation within each quintile was calculated for the selected conditions. SETTING: The study involved all 192 English district health authorities, but 57 were excluded because the proportion of unspecified diagnoses exceeded 5%. PATIENTS: The analyses were based on 336,799 cases from 135 districts. MEASUREMENTS AND MAIN RESULTS: Discharge ratios for the medical conditions and one surgical condition were significantly correlated with the levels of total discharge rates (p less than 0.01). The medical conditions showed greater systematic variation in discharge ratios than the surgical conditions. There was no consistent pattern in the values of systematic variation for the selected conditions across the different levels of discharge ratios for all conditions. CONCLUSIONS: It is argued that the changes in the NHS introduced in April 1991 are intended to introduce greater equity in the standardised discharge ratios and increase the total numbers of discharges. The results of this analysis suggest that, even if these objectives were achieved, they may not result in increased levels of elective care, nor result in greater equity in terms of rates of discharge for individual conditions.

Acute Disease↗

Associations of excessive irritability with common illnesses and food intolerance.

In a national study of almost 7000 primary school children, parents' perceptions were used to test the hypothesis that the child's irritability was associated with food intolerance independently of other symptoms. After adjustment in a multiple regression analysis for asthma or wheeze, cough, eczema, hives, diarrhoea and vomiting, rhinitis, hay fever and headache, and the social factors of father's social class, maternal education and maternal age, a highly significant association between perception of food intolerance and irritability (P less than 0.001) remained. Though we cannot rule out that irritable children's parents could be biased towards diagnosing food intolerance the possibility that some children do have behavioural disturbance associated with reactions to food needs to be explored further, preferably with a double blind challenge assessment.

Affect↗

Sleep habits and height at ages 5 to 11.

Shorter durations of slow wave sleep and lower growth hormone responses have been reported in children with short stature caused by psychosocial deprivation. We investigated whether lower total sleep duration was associated with shorter stature in a sample of children taking part in the National Study of Health and Growth. Parental responses to a self administered questionnaire were used to estimate usual times for going to sleep at night and usual times for waking in the morning for 5145 children aged 5 to 11 years of age. After adjusting for the effects of other variables known to be associated with height, it was shown that there was a weak negative association between sleep duration and height. It is concluded that variation in sleep duration between children is unlikely to have an important influence on growth.

Body Height↗

Need for new reference curves for height.

Data from the National Study for Health and Growth, on children aged from 4.0 to 12.0 years measured in 1972, 1985, and 1986 were used to assess whether new growth standards are required, and which subgroups of children might require separate standards. The change over this period, from just over half a centimetre in the youngest girls to over a centimetre in the oldest boys, warrants the use of revised reference curves, which are also needed for Afro-Caribbean children.

Body Height↗

Height of primary school children and parents' perceptions of food intolerance.

In the national study of health and growth parents' responses to a self completed questionnaire were used to categorize children according to their experience of food intolerance. The heights of the children in each group were then compared. Useful responses to the questions on food intolerance were received for 6813 (85%) children in the sample and measurements of height obtained for 7856 (98%). Children with food intolerance were shorter than other children. A difference in height of about 1.5 cm remained after adjusting for social and biological factors and some common symptoms in childhood using multiple regression. The number of different types of food avoided was associated with shortness in the food intolerant group but not in the non-food-intolerant group. Regardless of the underlying aetiology, these findings suggest that parents' complaints of food intolerance in their children should be taken seriously.

Body Height↗

Repeatability of a questionnaire to assess respiratory symptoms in smokers.

To evaluate the repeatability of a questionnaire designed to assess change in respiratory symptoms 90 smokers were interviewed on two occasions. The questionnaire included questions from the Medical Research Council questionnaire on respiratory symptoms, questions on acute chest illness and cough and phlegm production in the preceding two weeks, a modification of Field's card system for estimating frequency of cough, and an objective assessment of the presence of phlegm--the loose cough sign. The study was carried out in two parts. During the first part 30 male smokers were interviewed by one observer and then re-interviewed 1 to 2 hours later by a different observer. During the second part 60 subjects were interviewed and then after a period of 1 to 10 days re-interviewed by the same observer. The results showed that the within-subject variation representing the measurement error for Field's card system was 15.1% of the between-subject variation and was adequately Normal to justify the use of standard analytical techniques. Similar results were obtained from questions on cough and phlegm scored between 1 and 5, although the variation in this case was rather less Normal. In general, the between-observer, within-observer, and within-subject repeatability were satisfactory for all parts of the questionnaire with the exception of the loose cough sign which had a relatively low prevalence. There was no evidence of an observer order effect and there were no important systematic differences due to lapses in time or different observers.The findings indicate that the techniques such as the cough scoring system may be used to permit studies of respiratory symptoms via questionnaire methods to be much smaller than those required to detect equivalent differences in prevalences.

Adult↗

The metabolic fate of N-isopropyl-N-phenyloxamic acid in the rat and the milk goat.

Rats excreted the 14C from a single oral dose of N-isopropyl-N-[14C]phenyloxamic acid [I, a soil metabolite from 2-chloro-N-isopropylacetanilide (propachlor)] in approximately equal quantities in the urine (49.2%) and feces (48.2%). A milking goat given daily oral doses of [14C]-I (1 mg of I three times daily) excreted more 14C in the feces (56.6%) than it excreted in the urine. From both species, I accounted for 97 to 100% of the urinary 14C, and all of the 14C that was extractable from the feces (73 to 75% of the 14C in feces was extractable with methanol). Goat milk samples collected 16 hr after the last dose contained no detectable 14C. Tissue residues of 14C were determined.

Amino Acids↗

Metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) administered topically to a sheep.

A sheep dosed topically with 14C-crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) excreted 45.5% of the 14C dose in the urine within 9 days. The feces contained 1.2% and the carcass 40.4% (this included the 37.7% of the dose remaining on the skin in the dosing area) of the dose. At sacrifice, the fat, liver, kidney, lung, and skin (where the dose was applied) contained the highest concentrations of 14C. Fourteen urinary metabolites were isolated and characterized by mass spectrometry. The metabolic reactions involved were oxidations of the t-butyl moiety, O-demethylation, replacement of the H-N-CH3 moiety with a hydroxyl group, oxidation of the N-methyl group to yield N-formyl phosphoramidates, hydrolysis of the phosphoramidate moiety to yield phenols, conjugation with glucuronic acid and combinations of these reactions.

Administration, Topical↗

Metabolism of 2-chloro-N-isopropylacetanilide (propachlor) in the rat.

Eleven urinary metabolites from [14C]propachlor were either identified or characterized by mass spectrometry. Those identified were 2-[S-(N-acetyl)cysteinyl]-N-isopropylacetanilide, 2-(methylsulfonyl)-acetanilide, 4'-hydroxy-2-(methylsulfonyl)-acetanilide, and 4'-hydroxyacetanilide. Those characterized were N-(1-hydroxyisopropyl)-2-(methylsulfonyl) acetanilide and its glucuronide, the glucuronides of 4'-hydroxy-N-isopropyl-2-(methylsulfonyl)acetanilide, N-(1-hydroxyisopropyl) aniline, 4'-hydroxy-2-(methylsulfonyl)acetanilide, and either N-(1-hydroxy-isopropyl) acetanilide or 2-hydroxy-N-isopropylacetanilide.

Acetanilides↗

Metabolism of crufomate [(4-tert-butyl-2-chlorophenyl methyl methylphosphormidate)] by the rat.

Fifteen metabolites of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate, I) were identified in the excreta from rats given single oral doses of I. Compound I was not detected in either the urine or the feces. The metabolic reactions observed were N-and O-demethylation, oxidations of the t-butyl moiety, replacement of the H-N-CH3 with an OH moiety, hydrolysis of the phosphoramidate moiety to yield the phenol, conjugation with glucuronic acid, and combinations of these reactions. No ring dehalogenation or ring substitution was observed.

Animals↗

Rat intestinal metabolism of crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate).

Everted sacs of rat small intestine metabolized crufomate (4-tert-butyl-2-chlorophenyl methyl methylphosphoramidate) under in vitro conditions to form six 14C-labeled metabolites in quantities sufficient for isolation and identification. These metabolites were 4-tert-butyl-2-chlorophenyl methyl phosphoramidate (25%), 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenyl methyl methylphosphoramidate (19%), 2-[3-chloro-4-[[(methoxy) (methyl-amino)phosphoinyl]oxy]phenyl]-2-methylpropionic acid (2%), 4-tert-butyl-2-chlorophenol (0.8%) and its glucuronide (6%), and the aromatic glucuronide of 2-chloro-4(2-hydroxy-1,1-dimethylethyl)phenol (1%). These intestinal metabolites may represent precursory stages in the overall metabolism of crufomate.

Animals↗

Replacement of a chlorine with a methylsulfonyl group in the metabolism of propachlor (2-chloro-N-isopropylacetanilide).

Urine from rats and sheep given single doses of [14C]propachlor contained 14C metabolites in which the chlorine of propachlor was replaced by a methylsulfonyl group. Methylsulfonyl-containing metabolites were also isolated from the urine of rats given an intraperitoneal dose of the cysteine conjugate of [14C]propachlor; this indicated that the methylsulfonyl-containing metabolites resulted from metabolic reactions subsequent to the mercapturic acid pathway.

Acetamides↗