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Biomedical subjects

K Davies

Publications and source records attributed to K Davies.

At least 55 records · Page 3Linked to original sources
PubMed1998

Genetic and acquired predisposing factors and treatment of osteoporosis in thalassaemia major.

We have previously shown a high incidence of osteopenia and osteoporosis in patients with thalassaemia major. These bone changes, were more severe in males than females, in those with diabetes mellitus and with hypogonadal-hypogonadism. Our recent studies concern the relationship of erythroid activity, assessed by serum transferrin receptors as an overall measure of anaemia, to osteoporosis. Serum transferrin receptor levels correlated with the mean pre-transfusion haemoglobin level, but there was no correlation with the incidence of osteopenia and osteoporosis. As osteoporosis has a strong genetic component we have also studied the COLIA1 and COLIA2 genes which code for the major protein of bone (type 1 collagen). Studies by others have shown in non-thalassaemic patients that a polymorphism G-->T or TT in a regulatory region of COLIA1 at the recognition site for transcription factor Sp1 is associated with the presence of osteoporosis. Our studies suggest that Sp1 polymorphism is not specific to any one ethnic group; the polymorphism occurs more commonly in females (female to male ratio 2:1). In male thalassaemia major patients the presence of the Sp1 mutation was associated with more severe osteoporosis of the spine and the hip compared with female patients. There is failure of improvement in spinal osteoporosis with bisphosphonate therapy (intravenous Pamidronate) in male patients with the Sp1 mutation.

Adolescent↗
PubMed1998

Nutrient recovery and biodegradation of inedible tomato plant residues by activated sludge cultures and Phanerochaete chrysosporium.

The biodegradation of inedible biomass and the recovery of nutrients from hydroponically grown tomato plant material were investigated under various growth conditions of activated sludge and the fungus Phanerochaete chrysosporium. The experiments were carried out in shaker flasks at three incubation temperatures (25 degrees C, 40 degrees C, and 60 degrees C for the activated sludge and 25 degrees C, 40 degrees C, and 50 degrees C for the fungi) with heat-pretreated samples at 150 degrees C for 30 min, and without pretreatment of the inedible residues. Under the experimental conditions tested, both cultures exhibited similar performance in terms of solids reduction and nutrient recovery. Solids reduction as high as 70% was obtained in both systems. Most of the solids degradation occurred the first 16 days of incubation. Cellulose degradation reached about 90% but no significant reduction in the solids lignin content was observed. Recovery of nitrogen (as NO2-N and NO3-N) and other micronutrients was sufficiently high and was accompanied by an average 70% reduction in COD, indicating that the final effluent is suitable for hydroponic plant growth. Incubation temperature had a minimal effect on solids degradation but appeared to influence the leachability of certain nutrients.

Bacteria↗
PubMed1997

Neuropsychological characteristics of the syndrome of mesial temporal lobe epilepsy.

OBJECTIVE: To identify the neuropsychological features of the syndrome of mesial temporal lobe epilepsy (MTLE), a surgically remediable epileptic syndrome defined by the presence of hippocampal sclerosis, using a broad and comprehensive neuropsychological test battery. SETTING: Epilepsy surgery center. PATIENTS: After scalp adn invasive electroencephalographic monitoring, a consecutive series of 107 adults were found to have intractable complex partial seizures of unilateral left (n = 62) or right (n = 45) temporal lobe origin. Patients were included if they were not retarded and had left hemisphere dominance for speech but no magnetic resonance imaging abnormalities other than hipocampal sclerosis. Histopathological analyses of resected hippocamppi showed that 66 patients had hippocampal sclerosis (MTLE+), and 41 did not have evidence of significant hippocampal sclerosis (MTLE-). INTERVENTIONS: None. MAIN DEPENDENT MEASURES: A comprehensive battery of neuropsychological tests that included measures of intelligence, academic achievement, language, visuoperceptual or visuospatial function, memory and learning, attention, and problem-solving abilities. RESULTS: The syndrome of MTLE was associated with considerable generalized cognitive impairment (in intelligence, academic achievement, language, and visuospatial functions), but not related to adequacy of performances in other selected cognitive domains (attention or concentration, executive functions). Material-specific memory effects were obtained-primarily for verbal memory in association with left-sided MTLE. CONCLUSIONS: Distinct neuropsychological features of spared, compromised, and laterality-specific cognitive impairments characterize the syndrome of MTLE. This information needs to be incorporated into formal syndrome criteria.

Adult↗
PubMed1997

Reorganization of verbal memory function in early onset left temporal lobe epilepsy.

The purpose of this investigation was to examine the issue of reorganization of verbal memory function following early insult to the left mesial temporal region. It was hypothesized that reorganization of memory function was most likely to occur in those patients with an early age of seizure onset who have a more limited degree of extra-hippocampal neuropathology. Fifty-four patients with epilepsy of unequivocal left temporal lobe origin were classified into four groups on the basis of the presence/absence of hippocampal sclerosis and degree of postoperative seizure relief. Measures of verbal learning and memory as well as nonmemory measures were administered both before and 6 to 8 months after anterior temporal lobectomy. Findings were consistent with the reorganization proposal. The clinical and theoretical significance of the findings are discussed.

Adult↗
PubMed1997

Influence of proxy respondents and mode of administration on health status assessment following central nervous system tumours in childhood.

Central nervous system (CNS) tumours account for 20% of childhood cancers. Survivors often experience severe physical, neuropsychological and social sequelae of the disease and its treatment. Health status assessment in these individuals is an essential clinical outcome measure, yet little consensus exists regarding the optimum methodology. The influence of proxy respondents (parents, physiotherapists and doctors) and mode of administration (home and clinic) in which assessments is performed has been evaluated in a cohort of 37 survivors of childhood CNS tumours. A health-related quality of life (HRQOL) questionnaire, incorporating the Mark II and III Health Utilities Indices, was completed at home and in clinic by patients and parents. Doctors and physiotherapists completed this questionnaire plus Lansky Play-Performance and Karnofsky Performance scores. No significant differences between raters for single attribute scores occurred either at home or in clinic, although a wide range of agreement (kappa = 0.05-1.00, percentage agreement 53-100%) between observers was revealed. Most agreement occurred between parents and patients: this was greatest on home completion (kappa = 0.48-1.00, percentage agreement 53-100%). Doctors and physiotherapists agreed less on subjective attributes (emotion, cognition and pain). Better if responses were classified as normal and abnormal. Inter-observer agreement was greater for the HRQOL questionnaire than for Karnofsky and Lansky scores. Home completion of questionnaires provides a reliable, acceptable and convenient method of assessing health status.

Adolescent↗
PubMed1997

Expression of truncated utrophin leads to major functional improvements in dystrophin-deficient muscles of mice.

Dystrophin-deficient mice (mdx) expressing a truncated (trc) utrophin transgene show amelioration of the dystrophic phenotype. Here we report a multifunctional study demonstrating that trcutrophin expression leads to major improvements of the mechanical performance of muscle (that is, force development, mechanical resistance to forced lengthenings and maximal spontaneous activity) and of the maintenance of the intracellular calcium homeostasis. These are two essential functions of muscle fibers, known to be impaired in mdx mouse muscles and Duchenne muscular dystrophy (DMD) patients. Our results bring strong support to the hypothesis that muscle wasting in dystrophin-deficient DMD patients could be prevented by upregulation of utrophin.

Animals↗
PubMed1997

Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype.

Autosomal recessive spinal muscular atrophy (SMA) is classified, on the basis of age at onset and severity, into three types: type I, severe; type II, intermediate; and type III, mild. The critical region in 5q13 contains an inverted repeat harboring several genes, including the survival motor neuron (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44 gene, which encodes a transcription-factor subunit. Deletion of NAIP and p44 is observed more often in severe SMA, but there is no evidence that these genes play a role in the pathology of the disease. In > 90% of all SMA patients, exons 7 and 8 of the telomeric SMN gene (SMNtel) are not detectable, and this is also observed in some normal siblings and parents. Point mutations and gene conversions in SMNtel suggest that it plays a major role in the disease. To define a correlation between genotype and phenotype, we mapped deletions, using pulsed-field gel electrophoresis. Surprisingly, our data show that mutations in SMA types II and III, previously classed as deletions, are in fact due to gene-conversion events in which SMNtel is replaced by its centromeric counterpart, SMNcen. This results in a greater number of SMNcen copies in type II and type III patients compared with type I patients and enables a genotype/phenotype correlation to be made. We also demonstrate individual DNA-content variations of several hundred kilobases, even in a relatively isolated population from Finland. This explains why no consensus map of this region has been produced. This DNA variation may be due to a midisatellite repeat array, which would promote the observed high deletion and gene-conversion rate.

Centromere↗
PubMed1997

Clinical, cytogenetic, and molecular analysis of three families with FRAXE.

The probe StB12.3 has been used to screen the FMR-1 gene in 42 pedigrees with a distal Xq fragile site for expansion of the CCG repeat and aberrant methylation of the FRAXA locus. Four families did not have a FRAXA mutation and were investigated further. Fluorescent in situ hybridisation (FISH) and molecular analyses showed that three of these families had an expansion at FRAXE and one at FRAXE. Detailed psychiatric, psychological, and behavioural features of three families with FRAXE identified in the study are presented. All the males who expressed FRAXE had a large methylated CCG repeat at FRAXF. All males with the mutation had some degree of mental handicap. This study illustrates the need for the FRAXE phenotype to be defined further.

Adult↗
PubMed1996

The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases.

The mitogen-activated protein (MAP) kinase family includes extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) and p38/RK/CSBP (p38) as structurally and functionally distinct enzyme classes. Here we describe two new dual specificity phosphatases of the CL100/MKP-1 family that are selective for inactivating ERK or JNK/SAPK and p38 MAP kinases when expressed in COS-7 cells. M3/6 is the first phosphatase of this family to display highly specific inactivation of JNK/SAPK and p38 MAP kinases. Although stress-induced activation of p54 SAPKbeta, p46 SAPKgamma (JNK1) or p38 MAP kinases is abolished upon co-transfection with increasing amounts of M3/6 plasmid, epidermal growth factor-stimulated ERK1 is remarkably insensitive even to the highest levels of M3/6 expression obtained. In contrast to M3/6, the dual specificity phosphatase MKP-3 is selective for inactivation of ERK family MAP kinases. Low level expression of MKP-3 blocks totally epidermal growth factor-stimulated ERK1, whereas stress-induced activation of p54 SAPKbeta and p38 MAP kinases is inhibited only partially under identical conditions. Selective regulation by M3/6 and MKP-3 was also observed upon chronic MAP kinase activation by constitutive p21(ras) GTPases. Hence, although M3/6 expression effectively blocked p54 SAPKbeta activation by p21(rac) (G12V), ERK1 activated by p21(ras) (G12V) was insensitive to this phosphatase. ERK1 activation by oncogenic p21(ras) was, however, blocked totally by co-expression of MKP-3. This is the first report demonstrating reciprocally selective inhibition of different MAP kinases by two distinct dual specificity phosphatases.

Amino Acid Sequence↗
PubMed1996

The effects of human hippocampal resection on the serial position curve.

The purpose of this study was to examine the contribution of the human hippocampal formation to the classic serial position curve. Seventy-seven patients who underwent anterior temporal lobectomy (ATL) (47 left, 30 right) were administered a list learning task before and after surgery, and changes in the serial position curve were examined. Forty nonsurgical patients with complex partial seizures were tested at comparable intervals and served as controls. Changes in the serial position curve were seen only after left ATL, and almost exclusively among patients without hippocampal sclerosis. Patients without left hippocampal sclerosis, and who therefore underwent resection of hippocampus that was to a considerable degree structurally (and presumably functionally) intact, showed significant declines in recall from the primacy and middle portions of the list compared to all other groups. There was no change in the recency portion of the list. Patients with left hippocampal sclerosis showed only a modest decline in recall from the middle region compared only to the control group, and the right ATL groups did not show any significant changes in serial position recall. These findings demonstrate the contribution of the left hippocampus to those discrete portions of the serial position curve which rely on secondary memory, and have implications for assessing the effects of ATL on memory function.

Adult↗
PubMed1996

Evidence that a locus for familial psoriasis maps to chromosome 4q.

Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

Chromosome Mapping↗
PubMed1996

Evidence for compound heterozygosity causing mild and severe forms of autosomal recessive spinal muscular atrophy.

Spinal muscular atrophy is an autosomal recessive disease of motor neurone degeneration which shows a variable phenotype. Two candidate genes show deletions in affected subjects but with no distinction between different forms of the disease. We report an unusual family in which mild and severe SMA coexists and patients are deleted for the SMN gene. The father is affected with late onset SMA; therefore this family shows pseudodominant inheritance. When typed using closely linked flanking markers the severely affected son does not share the same haplotype as his sib, who is deleted for SMN but shows no signs yet of SMA. This supports the hypothesis that differences in SMA phenotype can be explained by a multiple allele model.

Adult↗