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Biomedical subjects

K Day

Publications and source records attributed to K Day.

At least 37 records · Page 2Linked to original sources

Cloning, expression and genomic organization of human placental protein disulfide isomerase (previously identified as phospholipase C alpha).

Phosphoinositol-specific Phospholipase C plays an important role in transducing receptor generated signals to the rest of the cell. A cDNA encoding a phospholipase has been described (Bennett et al., 1988, Nature 334, 268-270). However it is probable that this cDNA in fact encodes a protein disulfide isomerase. Since the original work suggested that this enzyme was important in the reproductive tract we sort to clone, sequence, express and characterize the recombinant protein isolated from the placenta. We have cloned and sequenced the cDNA encoding the human homolog of this cDNA from human placenta, although the mRNA was widespread in the female reproductive tract. We have transiently expressed it in both COS cells and also 1BR fibroblasts. Cell lysates were assayed for increased phospholipase activity and protein disulfide activity. We describe the entire cDNA sequence which is highly conserved between species. We have also cloned a portion of the genomic gene and described the intron/exon boundaries. In vitro translation of this cDNA showed that it encoded a protein of 61 kD with a cleavable signal peptide. Transient expression showed the protein produced had no phospholipase activity but did show protein disulfide isomerase activity. The expression work shows that this cDNA indeed encodes a protein disulfide isomerase and not a phospholipase. The nucleotide sequence shows marked conservation of the coding and regulatory regions which may suggest that this enzyme has evolved to perform a highly specialized function.

Base Sequence↗

The correlation between the intake of lutein, lycopene and beta-carotene from vegetables and fruits, and blood plasma concentrations in a group of women aged 50-65 years in the UK.

The correlations between the mean of 4 d weighed intakes of lutein, lycopene and beta-carotene and mean plasma concentrations during each of the four seasons were lutein r 0.64, lycopene r 0.47 and beta-carotene r 0.45. Intake was not significantly correlated with plasma concentrations during every seasonal time-point. There was a significantly higher intake of lutein during the spring compared with summer and autumn, lycopene intake was significantly higher during the summer and autumn and there were no significant seasonal differences in beta-carotene intake. There were, however, significant seasonal differences in plasma carotenoid concentrations, the highest levels occurring between May and October. There were large inter- and intra-individual variations in intake and plasma concentrations of carotenoids. BMI was inversely correlated with plasma beta-carotene (r-0.41). The findings suggest that plasma carotenoid concentrations are indicative of dietary intake, but the large intra-individual variation in plasma concentrations indicates that any assessment of longer-term status from data at any one time-point should be treated with caution.

Aged↗

Plasmodium falciparum: parasites defective in early stages of gametocytogenesis.

Some molecular characteristics of Plasmodium falciparum lines which do not produce gametocytes are described. Parasites carrying a subtelomerically deleted chromosome 9 cannot form even the earliest forms of gametocytes, detectable with antibodies against the gametocyte-specific antigen Pfg27. In a parasite culture of clone HB3, in which both intact and deleted forms of chromosome 9 are present, full-length chromosome 9 molecules are retained mainly in gametocytes. These data suggest that the subtelomeric portion of chromosome 9 is required at an early stage of gametocytogenesis. Parasite subclones derived from gametocyte producing clone 3D7, which completely lost ability to produce gametocytes, are also described. Unlike the previous gametocyteless lines, these parasites stably maintain a full-length chromosome 9 and the ability to cytoadhere to C32 melanoma cells after prolonged asexual propagation. Their defect in sexual development is therefore genetically and functionally distinct from that of parasites carrying a deleted chromosome 9. Gametocyteless subclones derived from 3D7 do not produce any Pfg27 mRNA, while this gene is anomalously expressed in asexual stage parasites of two lines of a different genetic background, 1776sel8 and C10, one able and the other unable to produce gametocytes.

Animals↗

Apolipoprotein E epsilon 2 allele promotes longevity and protects patients with Down's syndrome from dementia.

Although individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the epsilon 4 allele having been shown to be associated with the disease and, at least in some cases, the epsilon 2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the epsilon 2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.

Age of Onset↗

Mapping the genetic locus implicated in cytoadherence of Plasmodium falciparum to melanoma cells.

Many lines of Plasmodium falciparum undergo a deletion of the right end of chromosome 9 during in vitro cultivation accompanied by loss of cytoadherence to melanoma cells. The deletion also results in loss of expression of PfEMP1, the putative cytoadherence ligand, suggesting that PfEMP1 or a regulatory gene controlling PfEMP1 expression is encoded in this region. Initially a library of short fragments highly enriched for the right arm of chromosome 9 was constructed in bacteriophage lambda. Clones from this library were obtained randomly by the polymerase chain reaction (PCR) technique, sequenced and used to screen a yeast artificial chromosome (YAC)-P. falciparum library by PCR so that the region could be cloned and physically mapped in detail. We have used probes from this region to demonstrate that clones derived from ITG2 have undergone a deletion of intermediate length on chromosome 9. This could explain the unusual stability of cytoadherence in these clones.

Animals↗

Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records.

Women (n 160) aged 50 to 65 years were asked to weigh their food for 4 d on four occasions over the period of 1 year, using the PETRA (Portable Electronic Tape Recorded Automatic) scales. Throughout the year, they were asked to complete seven other dietary assessment methods: a simple 24 h recall, a structured 24 h recall with portion size assessments using photographs, two food-frequency questionnaires, a 7 d estimated record or open-ended food diary, a structured food-frequency (menu) record, and a structured food-frequency (menu) record with portion sizes assessed using photographs. Comparisons between the average of the 16 d weighed records and the first presentation of each method indicated that food-frequency questionnaires were not appreciably better at placing individuals in the distribution of habitual diet than 24 h recalls, due partly to inaccuracies in the estimation of frequency of food consumption. With a 7 d estimated record or open-ended food diary, however, individual values of nutrients were most closely associated with those obtained from 16 d weighed records, and there were no significant differences in average food or nutrient intakes.

Diet Records↗

Mental and physical health and ageing in mental handicap: a review.

With some exceptions, the mental and physical health problems of elderly mentally handicapped people are similar to those of the elderly population as a whole. Psychiatric disorder is more common due to a higher frequency of behaviour disorders. Increased longevity has been accompanied by a progressive increase in deaths from age-related conditions and in individuals with Down's syndrome exposed a predisposition to premature senility and dementia. Service issues include general health care, preventive measures, provision for those with psychiatric and age-related problems, and staff training.

Adult↗

Male mentally handicapped sex offenders.

BACKGROUND: Sex offences are overrepresented in the mentally handicapped, but information about the characteristics and offence behaviour of this group is limited. METHOD: A retrospective case note survey was made of 47 male patients referred for antisocial sexual behaviour. RESULTS: Of 191 offences and/or incidents committed, 55.5% were heterosexual, 24% indecent exposure, 12.4% homosexual, 13.6% serious and 3.6% involved physical assault. Average age of the offenders was 23.9 years, with a mean IQ of 59.5, and there was a high prevalence of family psychopathology, psychiatric illness, minor physical disabilities, sexual experience, impaired relationship skills and sexual recidivism. Recidivists showed a low specificity for offence type and age and sex of victim. Categorical analysis differentiated a 'sex offences only' group from a 'sex plus other offences' group in the key areas of psychopathology, offence behaviour and outcome; this was supported by factor analysis. CONCLUSION: The finding of two subgroups of mentally handicapped male sex offenders has important implications for prevention, assessment and treatment.

Adolescent↗

The S-antigen of Plasmodium falciparum: repertoire and origin of diversity.

S-antigens are heat-stable, highly polymorphic proteins released by Plasmodium falciparum at the time of schizont rupture. Previously determined S-antigen sequences allowed the proposal of a general gene structure consisting of 5 sequence blocks. The sequence of the central block of tandem repeats provides a useful means of distinguishing the S-antigen allele and also its serotype, whereas the amino and carboxy terminal sequences defined the S-antigen family, 4 of which have been described. We present the sequence of 3 new S-antigen alleles, for the isolates HB3, KF1916 and KF1917. The allele-defining repeat sequence is ETGPGKAGEQG for HB3, GDQTEGS(S/A)GGK for KF1917 and AGSNE(E/K) for KF1916. The sequences of these newly described S-antigens are consistent with the proposed general gene structure and all belong to defined families, although carboxy-terminal sequences appear to be much more variable within a family than previously realised.

Alleles↗

Detection of Lewy bodies in Trisomy 21 (Down's syndrome).

The presence of cortical senile plaques and neurofibrillary tangles sufficient to warrant a neuropathological diagnosis of Alzheimer's disease is well established in middle-aged individuals with Trisomy 21 (Down's syndrome). In contrast a relationship between Down's syndrome and Lewy bodies, one of the major neuropathological features of Parkinson's disease, has not been previously reported. In a clinico-neuropathological survey of 23 cases of Down's Syndrome, two patients, aged 50 and 56 years respectively, were found to have Lewy body formation in the substantia nigra in addition to cortical Alzheimer-type pathology. Neither case showed significant substantia nigra neuron loss although locus coeruleus loss was present in both. Since substantia nigra Lewy bodies are a characteristic neurohistological feature of idiopathic Parkinson's disease, their occurrence in cases of Down's syndrome with evidence of Alzheimer-type pathology supports an aetiopathological connection between Parkinson's disease, Alzheimer's disease, and Down's syndrome; and suggests that common pathogenic mechanisms may underlie aspects of neuronal degeneration in these three disorders, some of which may relate to aberrant chromosome 21 expression.

Adult↗

Comparison of single-dose diethylcarbamazine and ivermectin for treatment of bancroftian filariasis in Papua New Guinea.

This double-blind study compared the clinical safety and parasitologic efficacy of single-dose regimens of diethylcarbamazine (DEC) and ivermectin for treatment of bancroftian filariasis in Papua New Guinea. Five groups of 10 men each with mean levels of parasitemia ranging from 2,985 to 5,185 microfilariae (mf)/ml were given DEC (6 mg/kg of body weight one time or 1 mg/kg, then 6 mg/kg four days later) or ivermectin (220 micrograms/kg; 20 micrograms/kg, then 200 micrograms/kg four days later or 20 micrograms/kg, then 400 micrograms/kg four days later). No significant side effects (e.g., acute adenolymphangitis, fever lasting more than eight hours, hypotension) were observed in any of the five treatment groups. The magnitude of reduction in microfilaremia was greater (P < 0.01) for the three ivermectin groups versus the two DEC groups in the first 30 days after drug administration (mf levels < 1% of pretreatment values versus 22.6-41.5%, respectively). At 90 and 180 days, mf levels continued to decrease in the DEC groups whereas they increased in the ivermectin groups given a total dose of 220 micrograms/kg. Eighteen months after drug administration, individuals given DEC or 420 micrograms/kg of ivermectin had the greatest degree of reduction in microfilaremia (86-90% compared with the pretreatment values). Decreases in parasite antigenemia measured by enzyme-linked immunosorbent assay for a secreted 200-kD adult worm antigen were greatest for the single-dose DEC group (39.7% decrease relative to the pretreatment level versus 7.8-15.7% for the ivermectin groups). These results indicate that single-dose DEC and ivermectin are well-tolerated by Wuchereria bancrofti-infected individuals with high levels of microfilaremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Antigenicity of a protective recombinant filarial protein in human bancroftian filariasis.

A 92-kDa fusion protein that encodes amino acids 1-479 of a 62-kDa Brugia malayi antigen induces resistance to microfilariae in mice. The antigenicity of this recombinant protein was explored in asymptomatic residents of Wuchereria bancrofti-endemic areas of Papua New Guinea and Egypt. Unlike sera from individuals in nonendemic areas, sera from residents of endemic areas contained IgG3 antibodies (up to dilution 1:1280) reactive with the fusion protein. There was little or no recombinant antigen-specific IgG1, IgG2, IgG4, or IgE. The mean level of IgG3 antibodies to the amino acid 1-479 construct in sera of putatively "immune" adult Papua New Guineans and children in whom microfilaremia was < 4 parasites/mL of blood was not significantly different (P < .05) from those with > 1000 parasites/mL. These data indicate that the filarial antigen corresponding to the recombinant protein is highly immunogenic in naturally infected children and adults and that the isotype and magnitude of antibody reactivity with it do not correlate with the microfilaremic status of asymptomatic persons.

Adolescent↗

A hospital-based treatment programme for male mentally handicapped offenders.

The paper describes a special hospital-based treatment programme for male mentally handicapped offenders, comprising a package of practical and personal skills training coupled with a socialisation programme based on token-economy strategies within a controlled and structured environment. Twenty patients admitted to the programme and followed up after discharge for an average of 3.3 years were studied in detail. All had committed serious or persistent offences and showed a high level of psychosocial pathology. A good or fair response to the treatment programme was made by 85%, and 65% were judged well adjusted or reasonably well adjusted at last follow-up contact. A good outcome was associated with more than two years' in-patient care, a good response to the treatment programme and stable residential placement, regular occupation and regular supervision and support in the community. Offenders against the person (sex and assault) had a better prognosis than and showed other interesting differences from property offenders (property and arson).

Adolescent↗

An assessment of the chronic toxicity of the synthetic pyrethroid, fenvalerate, to Daphnia galeata mendotae, using life tables.

The effects of chronic exposure to fenvalerate, a synthetic pyrethroid insecticide, on the cladoceran Daphnia galeata mendotae were evaluated under laboratory conditions. The daphnids were exposed for their entire life cycle to concentrations ranging from 0.005 to 0.1 microg fenvalerate litre(-1). The parameters used to determined toxicity were survival, time to first reproduction, reproductive frequency, number of young per brood, cumulative brood size, intrinsic rate of natural increase (r(m)), generation time (T) and net reproductive rate (R(0)). A concentration of 0.005 microg fenvalerate litre(-1) resulted in an increase in longevity but a decrease in production of young. Higher concentrations caused a decrease in survival. Studies of shorter duration than the complete life cycle of the organisms would not have detected toxicity at such low levels. The intrinsic rate of natural increase, r(m), was not affected by fenvalerate until concentration reached 0.05 microg litre(-1) and r(m) decreased to 0.113 from 0.238. A concentration of 0.01 microg litre(-1) caused the net reproductive rate, R(0), and the generation time, T, to decrease to 73.2 offspring per female and 17.3 days from 125.9 offspring per female and 20.3 days, respectively.

Journal Article↗

Computer-assisted versus unassisted analysis of the exercise electrocardiogram in patients without myocardial infarction.

Computer-assisted interpretation of the exercise electrocardiogram has been advocated to improve the accuracy of diagnosing coronary artery disease. Its accuracy was compared with a blinded visual interpretation of exercise-induced ST depression in 271 consecutive subjects without prior myocardial infarction who were referred for coronary angiography. The sensitivity of the visual and computer readings was 0.51 and 0.51, respectively, at a specificity of 0.87. Receiver operating characteristic curves were generated for the visual and computer ST depression in lead V5. Analysis of the areas under these curves showed no significant difference between them, indicating that computer-assisted analysis was not superior to unmodified visual analysis. A similar analysis was applied to two other computer indexes reported to be superior to visual assessments (treadmill exercise score and ST index). These computer indexes were not superior to a conventional visual analysis of leads I, II, V2, V4 and V5 in predicting severe disease (greater than 50% luminal narrowing). These results suggest that computer-assisted interpretation does not improve the accuracy of exercise electrocardiography in diagnosing coronary artery disease in subjects without prior myocardial infarction.

Adult↗