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Biomedical subjects

J R Thompson

Publications and source records attributed to J R Thompson.

At least 145 records · Page 8Linked to original sources

A novel cis element essential for stimulated transcription of the p41 promoter of human herpesvirus 6.

The p41 DNA-binding protein of human herpesvirus 6 is an apparent processivity factor important for viral DNA replication. The p41 promoter was characterized to understand how this processivity factor is regulated. A single transcription start site and a functional TATA box are located 48 and 74 bp, respectively, upstream of the start codon. A reporter construct containing 1,027 bp of the sequence upstream of the p41 start codon was inactive in uninfected T cells but functioned as a strong promoter in human herpesvirus 6-infected cells. Mutational analysis identified a 21-bp element (the EA site) which is located at -73 to -52 bp relative to the transcription start site and is essential for promoter activity. The ability of the EA site to stimulate transcription optimally appears to be strictly dependent upon its distance from the p41 basal promoter. The EA site contains three overlapping sequences, a CAAT-enhancer-binding protein (C/EBP) transcription factor recognition site and two repeat elements. Mobility shift assays using the EA site identified four binding activities (C1 to C4). C1 and C2 are present in both uninfected and infected cells and do not contain C/EBP factors. In infected cells, point mutation of the EA site abrogates C1 and C2 binding activities and destroys transcriptional activity of the p41 promoter. C3 and C4 are present in uninfected cells only and were found to contain C/EBP factors. These findings indicate that in infected cells, transcriptional stimulation of the p41 promoter by the EA site requires C1 and C2 binding activities. These results further suggest that transcriptional activity may also depend upon the elimination of C3 and C4 binding activities.

Amino Acid Sequence↗

Pulmonary function in infants with cystic fibrosis: the effect of antibiotic treatment.

Since 1982 all infants born within the East Anglian Regional Health Authority have been screened for cystic fibrosis. Between April 1985 and April 1992 infants identified in this way have been entered into a randomised prospective controlled trial of antibiotic prophylaxis. Approximately half the infants received continuous oral flucloxacillin and the remainder received antibiotics when clinically indicated. Infants underwent tests of respiratory function at 3-4 months and at 1 year of age. Measurements of thoracic gas volume and airway conductance were made with an infant whole body plethysmograph, and maximum expiratory flow by the 'squeeze' technique. A total of 73 tests was performed of 42 infants. To facilitate comparisons, measurements were expressed as scores. The mean values of the scores for the two groups of infants fell within normal limits. There was no difference between the treatment groups at either age. A reduction in airways conductance was observed between the two tests.

Administration, Oral↗

Social deprivation and age at presentation in amblyopia.

BACKGROUND: Amblyopia is the most common visual disability in children. Early treatment is thought to be more effective, and therefore factors affecting the age at presentation are important. A relationship between social deprivation and access to health care and screening services is well known. We hypothesized that social deprivation might be associated with later presentation of amblyopia, particularly of anisometropic amblyopia which depends on vision screening for referral. METHODS: Data from a historical cohort of 897 children with amblyopia, from seven UK orthoptic clinics, were used to test this hypothesis. Social deprivation was measured by the Townsend score of the ward in which the child lived. RESULTS: A relationship between social deprivation and age at presentation was found in children with anisometropic amblyopia even after adjusting for differences between clinics (p = 0.01) but no similar association was evident in children with amblyopia associated with strabismus. There was a difference of 22 months in the average age at presentation between children with anisometropic amblyopia in the most deprived and least deprived areas of the study. CONCLUSIONS: If screening for anisometropic amblyopia is to be undertaken, priority should be given to screening children from areas of social deprivation.

Age Factors↗

The prevalence of eye disease in Leicester: a comparison of adults of Asian and European descent.

Random samples of people aged 40 years and over were drawn from lists of patients registered with two neighbouring inner-city general practices: one predominantly with Asian patients and the other predominantly with European patients. The people selected were invited to attend specially arranged eye clinics for examination by an ophthalmologist and an optician. We examined 377 people and found that, compared to people of European descent, Asians had a significantly higher prevalence of age-related cataract: 30% compared to 3% in people aged under 60 years and 78% compared to 54% in those aged 60 years and over. The age of onset of cataract seems to be earlier in Asians. After adjustment for age, there were no statistically significant ethnic differences in the prevalences of open-angle glaucoma, macular degeneration or diabetic retinopathy.

Adult↗

Osteosarcoma in a cow.

A mass involving the maxilla of a cow was determined to be an osteosarcoma. Microscopically, the mass was composed of plump pyriform cells aligned along thin trabeculae of osteoid. Osteosarcoma rarely develops in large animal species, but when it does, it is usually found in the skull and must be differentiated from more common diseases, such as actinomycosis and tooth abscesses.

Animals↗

Cataract and survival in an elderly nondiabetic population.

Follow-up ranging between 6 and 8 years of the survival of a cohort of 473 elderly nondiabetic subjects randomly selected from a small English town showed an age- and sex-adjusted association between nuclear cataract at the time of baseline examination and decreased survival (P = .002). Comparing those with and without nuclear cataract, the adjusted relative hazard for death was 1.52 (95% confidence interval, 1.15 to 1.99). This effect remained virtually unchanged when also adjusted for whether the subject reported ever having been a smoker.

Aged↗

Intratracheal pulmonary ventilation and congenital diaphragmatic hernia: a report of two cases.

Previous studies from our institution have shown that neonates with congenital diaphragmatic hernia (CDH), whose best postductal PaO2 (BPDPO2) was less than 100 mm Hg while on maximal conventional mechanical ventilation (CMV), had a mortality exceeding 90%. When combined with extracorporeal membrane oxygenation (ECMO), the mortality rose to 100% in those infants who developed hypercarbia following decannulation. Historically, those patients have required increasing ventilator support, leading to iatrogenic lung damage, and eventual death. Intratracheal pulmonary ventilation (ITPV) using the reverse thrust catheter (RTC) developed by Kolobow incorporates a continuous flow of humidified gas through a reverse Venturi catheter positioned at the distal end of the endotracheal tube. In animal studies, ITPV was shown to result in a reduced physiological dead-space (VD), to facilitate expiration, and to enhance CO2 elimination. In our current study, we have applied ITPV in two neonates with CDH who could not be weaned from ECMO because of uncontrollable hypercapnia, and who met above criteria for 100% mortality. In both cases, ITPV restored normal PaCO2 at low peak inspiratory pressure (PIP) with a substantial decrease in VD. We believe ITPV is suited to ventilating newborns with CDH in whom barotrauma is known to be common. Beyond its present use, ITPV may be useful to ventilate children with other forms of respiratory failure, and should be so considered along with other now available methods of mechanical pulmonary ventilation.

Hernia, Diaphragmatic↗

Comparison of the Keeler Pulsair 2000 non-contact tonometer with Goldmann applanation.

The Pulsair 2000 non-contact tonometer (Keeler Ltd, UK) is compared with the Goldmann applanation tonometer. Data from 80 eyes were acquired by four experienced observers. A linear regression analysis showed the relationship between the instruments to be: Pulsair = 0.66 + 0.95 Goldmann. Individual components of variation were analysed by analysis of variance which indicated a significant variation in the slope of the regression equation due to observers (p = 0.02) but not to the order in which topical anaesthesia was administered. Differences between two Pulsair instruments were of marginal significance (p = 0.07). The intercept of the regression equation was unaffected by any of the components of variation. Seventy-nine per cent of averaged intraocular pressure measurements obtained with the Pulsair 2000 fell on or within +/- 3 mmHg of those measured with the Goldmann tonometer. It is concluded that the Pulsair 2000 can provide clinically useful measurements of intraocular pressure.

Adolescent↗

The effect of a cold environment on protein and energy metabolism in calves.

Eleven Holstein bull calves 35 d of age were assigned to one of three treatment groups: (1) W72, warm environment (20 degrees), 72 g feed/kg body weight (BW)0.75 per d, (2) C72, cold environment (-5 degrees), 72 g feed/kg BW0.75 per d, or (3) C90, cold environment (-5 degrees), 90 g feed/kg BW0.75 per d. Fractional synthesis rates (FSR) of protein in the rumen wall, rumen papillae, omasum, duodenum, kidney, liver, heart, longissimus dorsi, biceps femoris and skin were determined following a continuous infusion of [3H]phenylalanine. Phenylalanine flux was elevated in both groups of cold-adapted calves. FSR of protein in the two muscles and skin were reduced along with N retention in the calves in the C72 group compared with the other two groups. Muscle protein degradation, estimated from urinary N tau-methylhistidine excretion, tended to be elevated in both groups of cold-adapted calves. Reduced protein synthesis and increased protein degradation in the C72 group contributed to reduced muscle protein gain. It appears that when feed intake is limited in cold-adapted animals, muscle and skin have a lower priority for nutrients than other organs and tissues, resulting in reduced protein synthesis. It seems unlikely that thermogenesis due to enhanced protein synthesis contributed to the increased heat production in the cold.

Adaptation, Physiological↗

Molecular genetics of cryptopleurine resistance in Saccharomyces cerevisiae: expression of a ribosomal protein gene family.

The Saccharomyces cerevisiae CRY1 gene encodes the 40S ribosomal subunit protein rp59 and confers sensitivity to the protein synthesis inhibitor cryptopleurine. A yeast strain containing the cry1-delta 1::URA3 null allele is viable, cryptopleurine sensitive (CryS), and expresses rp59 mRNA, suggesting that there is a second functional CRY gene. The CRY2 gene has been isolated from a yeast genomic library cloned in bacteriophage lambda, using a CRY1 DNA probe. The DNA sequence of the CRY2 gene contains an open reading frame encoding ribosomal protein 59 that differs at five residues from rp59 encoded by the CRY1 gene. The CRY2 gene was mapped to the left arm of chromosome X, centromere-proximal to cdc6 and immediately adjacent to ribosomal protein genes RPS24A and RPL46. Ribosomal protein 59 is an essential protein; upon sporulation of a diploid doubly heterozygous for cry1-delta 2::TRP1 cry2-delta 1::LEU2 null alleles, no spore clones containing both null alleles were recovered. Several results indicate that CRY2 is expressed, but at lower levels than CRY1: (1) Introduction of CRY2 on high copy plasmids into CryR yeast of genotype cry1 CRY2 confers a CryS phenotype. Transformation of these CryR yeast with CRY2 on a low copy CEN plasmid does not confer a CryS phenotype. (2) Haploids containing the cry1-delta 2::TRP1 null allele have a deficit of 40S ribosomal subunits, but cry2-delta 1::LEU2 strains have wild-type amounts of 40S ribosomal subunits. (3) CRY2 mRNA is present at lower levels than CRY1 mRNA. (4) Higher levels of beta-galactosidase are expressed from a CRY1-lacZ gene fusion than from a CRY2-lacZ gene fusion. Mutations that alter or eliminate the last amino acid of rp59 encoded by either CRY1 or CRY2 result in resistance to cryptopleurine. Because CRY2 (and cry2) is expressed at lower levels than CRY1 (and cry1), the CryR phenotype of cry2 mutants is only expressed in strains containing a cry1-delta null allele.

Alkaloids↗

High-resolution proton nuclear magnetic resonance spectroscopy in the detection of low molecular weight volatiles.

Proton nuclear magnetic resonance spectroscopy (1H MRS) has been used to identify ethanol in vivo and to detect other exogenous low molecular weight volatiles in human serum. 1H MRS was used to detect and quantitate 15 human sera containing various concentrations and combinations of ethanol, isopropanol, acetone, and methanol as previously quantitated by headspace gas chromatography. The 1H MRS method was linear for each alcohol. The lowest detectable alcohol concentration was 15 mg/L (peak height equal to three times the signal-to-noise ratio), and 30 mg/L (+/- 10% relative standard deviation) was the lowest level reproducibly quantitated. Within-run and day-to-day coefficients of variation (CV) ranged from 0.8 to 2.0% and 0.9 to 1.2%, respectively, for methanol; 0.5 to 1.9% and 0.6 to 1.3% for acetone; and 0.5 to 1.6% and 0.3 to 2.2% for isopropanol. In all cases, the lowest CVs for a particular compound were obtained for the highest measured concentration (1500 mg/L), and the highest CVs were observed for the lowest concentration (250 mg/L). The 1H MRS method for detection of these volatiles does not require sample pretreatment and is nondestructive, which allows for further analysis by other methods.

1-Propanol↗

Disseminated Strongyloides stercoralis infection.

A case of disseminated S stercoralis is an immunosuppressed patient manifested with diarrhea, a rash, and progressive respiratory insufficiency. The parasites were eradicated with thiabendazole despite continued steroid therapy, and the patient survived the hospitalization. The characteristics of S stercoralis allow it to be harbored within a host for prolonged periods of time, only to disseminate once cell-mediated immunity is suppressed. A diagnosis of strongyloidiasis should be considered in an immunocompromised patient with a petechial rash. Prompt diagnosis and initiation of thiabendazole therapy provides the greatest opportunity for patient survival. Secondary bacterial infections should be aggressively sought. Mortality from disseminated strongyloidiasis approaches 80%.

Aged↗

Identification of a DNA-binding protein of human herpesvirus 6, a putative DNA polymerase stimulatory factor.

A 41K early nuclear antigen (p41), expressed in human herpesvirus type 6 (HHV-6)-infected T cells, was cloned by screening a cDNA expression library with the anti-p41 monoclonal antibody (MAb) C5. When expressed in mammalian cells, the cloned p41 protein comigrated with the authentic p41 protein from HHV-6-infected cells and localized to the nucleus. HHV-6 p41 shares 44% sequence identity with the human cytomegalovirus (HCMV) DNA-binding protein, ICP36 (UL44 gene product); p41 binds to ssDNA with the same apparent affinity as ICP36. Since ICP36 has recently been shown to be an HCMV DNA polymerase-associated stimulatory factor, a similar function is suggested for p41.

Amino Acid Sequence↗

Accuracy of Goldmann tonometry in clinical practice.

The intra- and inter-observer variability of Goldmann applanation tonometry was studied in 8 hospital tonometrists, 4 of whom received brief revision training in tonometer use. Intraocular pressure (IOP) measurements were obtained from 16 glaucoma patients. Over a series of four readings taken from individual eyes, intraocular pressure did not significantly vary. However, a decline in IOP was observed when a second tonometrist obtained a further series of four readings from a previously measured eye. Mean pressures recorded by tonometrists who had received revision training were greater than those obtained by the untrained observers though this could be accounted for by two highly experienced individuals in the untrained group who tended to record low pressures. Comparisons of average readings obtained by two observers on the same eye showed that approximately one-quarter of measurements differed by 2 or more mmHg and approximately one-fifth by 3 or more mmHg.

Female↗

Chronic persistent asthma presenting to an accident and emergency department--compliance with B.T.S. guidelines.

Forty-six patients, known to suffer from asthma, attending an inner-city accident and emergency (A&E) department, were screened for the presence of chronic symptoms and their current treatment documented. The patients were asked if they knew their optimum peak expiratory flow rate (PEFR) or if they possessed a peak flow meter. The treatment being used by each of the 26 patients with evidence of chronic persistent asthma was compared to that as advised by the British Thoracic Society (B.T.S.) and it was found that only three patients were receiving adequate treatment. Most often the treatment regimes were suboptimal due to the absence of an inhaled anti-inflammatory agent. Patient awareness of their own PEFR or possession of a peak flow meter was uniformly low in both the well-controlled patients and those with chronic persistent asthma.

Administration, Inhalation↗

Prevalence and family risk of ulcerative colitis and Crohn's disease: an epidemiological study among Europeans and south Asians in Leicestershire.

The family history of patients identified during incidence studies in Leicestershire were investigated and the prevalence and comparative risks calculated; 1254 patients aged 15 to 80 years were sent a questionnaire about their family history. All cases with a positive family history were reviewed and confirmed cases included in the study. In Europeans the standardised prevalence of Crohn's disease was 75.8/10(5) and that of ulcerative colitis 90.8/10(5). The prevalence of Crohn's disease among South Asians was 33.2/10(5) and that of ulcerative colitis 135/10(5). The prevalence of Crohn's disease in Europeans was significantly greater than that in Hindus (chi 2 = 16, p < 0.001), while the prevalence of ulcerative colitis was significantly lower in Europeans than Hindus (chi 2 = 27, p < 0.001) and Sikhs (chi 2 = 4.4, p < 0.05). The comparative risk of developing ulcerative colitis in first degree relatives of Europeans patients with ulcerative colitis was increased by approximately 15, but the risk of Crohn's disease was not increased. The comparative risk of developing Crohn's disease among first degree relatives of patients with Crohn's disease was increased by up to 35, the comparative risk of ulcerative colitis was approximately 3. The risk among relatives of South Asian patients with Crohn's disease was not increased, but the risk of ulcerative colitis to relatives of patients with ulcerative colitis was. This study supports the view that Crohn's disease and ulcerative colitis arise in people with a genetic predisposition and exposed to some, as yet unknown, environmental factor.

Adolescent↗

The reliability of ultrasonographic assessment of neonatal hips.

Ultrasound scans were made of the hips of 209 neonates born consecutively over a two-week period. Of the 418 scans, 62 images were selected at random and 25 of these were duplicated to give a total of 87 scans. These static images were then presented to five experienced observers who each made nine different assessments and measurements. Interobserver and intraboserver agreement was calculated and expressed as kappa values. Our results showed poor reliability on both counts.

Anthropometry↗