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Biomedical subjects

K Dawson

Publications and source records attributed to K Dawson.

At least 19 recordsLinked to original sources
PubMed2005

Surface complexation of DNA with insoluble monolayers. Influence of divalent counterions.

DNA interacts with insoluble monolayers made of cationic amphiphiles as well as with monolayers of zwitterionic lipids in the presence of divalent ions. Binding to dioctadecyldimethylammonium bromide (DODAB) or distearoyl-sn-glycero-3-phosphocholine (DSPC) monolayers in the presence of calcium is accompanied by monolayer expansion. For the positively charged DODAB monolayer, this causes a decrease of surface potential, while an increase is observed for the DSPC monolayers. Binding to dipalmitoyl-sn-glycero-3-phosphocholine preserves most of the liquid expanded-liquid condensed coexistence region. The liquid condensed domains adopt an elongated morphology in the presence of DNA, especially in the presence of calcium. The interaction of DNA with phospholipid monolayers is ion specific: the presence of calcium leads to a stronger interaction than magnesium and barium. These results were confirmed by bulk complexation studies.

Animals↗
PubMed2004

Pure motor mononeuropathy with distal conduction block: an unusual presentation of multifocal motor neuropathy with conduction blocks.

OBJECTIVE: To report an hitherto undescribed presentation of Motor Neuropathy with Multifocal Conduction Block (MMNCB). METHODS: Description of two patients presenting with complete paralysis of the 3 heads of the trapezius muscle (case one) and progressive weakness of finger extension (case 2). RESULTS: Nerve conduction studies (NCS) established that the corresponding nerves were distally inexcitable. In the affected muscles, no voluntary activity was elicited in both patients with spontaneous activity noted in patient 2. Systematic NCSs documented an asymptomatic, partial conduction block (CB) in a median nerve forearm segment in both patients. Neurophysiological follow-up after a dramatic response to intravenous immunoglobulins demonstrated recovery of the initially unobtainable motor responses. CONCLUSIONS: This indicates that a complete, distal CB of the motor fibers destined to the trapezius muscle in patient 1, and to the extensor indicis proprius in patient 2, had caused the heralding deficits. SIGNIFICANCE: These findings underscore the possibility of distal CB in this disorder and the need for extensive NCSs, including asymptomatic nerves, for an accurate diagnosis.

Adult↗
PubMed2003

A non-lethal method for assessment of efficacy of antiparasitics against parasites in horses such as Anoplocephala perfoliata and Gasterophilus intestinalis.

Sourcing of horses naturally infected with parasites such as Anoplocephala perfoliata and Gasterophilus intestinalis for antiparasitic efficacy slaughter studies is often difficult, expensive, and usually excessive numbers of animals must be slaughtered before significant data can be obtained. To overcome this problem a "Modified Critical Treatment Method" was developed. This method does not require the horses to be sacrificed, but relies on the collection and processing of all faecal material containing expelled parasites from test animals. Efficacy is assessed by comparing, in the same horses, the numbers of parasites expelled with the test compound with the total numbers removed with test and reference endectocides. This, for the most part, means that farms that were previously unavailable, e.g. studs, can now be used for the collection of efficacy data.

Animals↗
PubMed2003

Multiple sclerosis is more prevalent in northern New Zealand than previously reported.

BACKGROUND: There have been no studies of multiple sclerosis (MS) prevalence from New Zealand (NZ) in the past two decades, and only one in a northern NZ district. Our impression was that the local prevalence of MS was higher than previously published data would suggest. There is limited access to new treatments for MS in NZ. AIMS: The present paper aims to: (i). measure the prevalence of definite and probable MS in the Bay of Plenty (BOP), a North Island province, (ii). compare this with previous NZ studies, (iii). study the profile of disability in this population-based group and (iv). determine the proportion of MS patients who receive government funding for modern drug treatment (beta-interferons). METHODS: Patients were identified from a geographically and demographically defined area of the North Island of NZ, using multiple sources of case ascertainment and modern diagnostic criteria. All clinical records were reviewed and data were supported by a telephone interview. All patients' eligibility for -government-funded treatment with beta-interferon was considered. RESULTS: Eighty-six patients were identified as residents in BOP, NZ, on 15 January 2001. Excluding 'possible' cases, this represented a prevalence of 50/105 (95% confidence interval 40-62/105). Half of the population-based cohort had a disability defined as 'moderate to severe' (i.e. aids needed to walk, unable to take more than a few steps, or worse). Eleven patients (13%) had a primarily progressive form of MS. Eleven patients (13%) had the relapsing--remitting form of the disease and qualified for -government-funded treatment with beta-interferon. CONCLUSION: The prevalence of MS in the defined region was twice as high as that reported from an adjacent area, the Waikato, 20 years previous. Our data will help to update NZ prevalence statistics and are of direct relevance to current funding issues for modern treatments which, in NZ, are presently limited to a proportion of patients with relapsing- remitting disease.

Adjuvants, Immunologic↗
PubMed2003

A study of stereotypic behaviours in Alzheimer's disease and frontal and temporal variant frontotemporal dementia.

OBJECTIVE: To document the prevalence and pattern of stereotypic behaviour in patients with Alzheimer's dementia and frontal and temporal variants of frontotemporal dementia. Secondly, to examine the relationship between stereotypic and other neuropsychiatric behaviours. METHODS: Patients with the following were studied; Alzheimer's disease (n=28), frontal variant frontotemporal dementia (fvFTD, n=18), and semantic dementia-the temporal lobe variant of FTD (n=13). All patients were assessed using the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination, Addenbrooke's Cognitive Examination, and the Clinical Dementia Rating scale. Patients were also rated on the newly devised Stereotypic and Ritualistic Behaviour (SRB) subscale, which was designed as an addendum to the NPI. RESULTS: There was no significant difference across diagnostic groups in terms of age, sex, or severity of cognitive deficits. The overall NPI was significantly higher in patients with fvFTD compared with the other two groups, but fvFTD and semantic dementia showed a similar, and significantly increased, prevalence of stereotypic behaviours on the SRB subscale. Within the FTD group as a whole these behaviours were more likely to be complex, whereas in Alzheimer's disease, when present, such behaviours tended to be more simple stereotypies or stimulus bound repetitive behaviours. Stereotypic behaviours were not correlated with either disease severity or the extent of cognitive impairment in the fvFTD group, but were in the other two diagnostic groups. CONCLUSION: Complex stereotypic behaviours are a core feature of the dementing syndrome in FTD and may reflect early and specific deficits in orbitofrontal circuitry and basal ganglia involvement.

Aged↗
PubMed2002

The prevalence of frontotemporal dementia.

OBJECTIVE: To estimate the prevalence of frontotemporal dementia (FTD) and other degenerative early-onset dementias in a geographically defined population. BACKGROUND: Early-onset dementia (at age <65 years) results in high psychiatric morbidity and caregiver burden. Prevalence figures are available for early-onset AD but not for FTD, a dementia that is almost invariably of early onset. METHODS: Case ascertainment was by review of case records of three specialist clinic databases and inpatient admissions at a university hospital in Cambridge, United Kingdom, for patients with dementia who were <65 years of age, living in Cambridge City or East or South Cambridgeshire (population 326,019) on May 30, 2000. All the relevant health services in the area were also contacted for potential cases. Diagnosis of various dementias was based on published criteria. All patients with potential FTD were examined by the study investigators and underwent structural neuroimaging. The 1998 population estimates for the area were used to calculate age and sex prevalence with confidence intervals for AD, FTD, and other causes of dementia. RESULTS: A total of 108 patients (66 men and 42 women) with dementia with onset before they were 65 years of age were identified, of whom 60 were <65 years on the census date, giving an overall prevalence of 81 (95% CI, 62.8 to 104.5) per 100,000 in the 45- to 64-year age group. The prevalences of early-onset FTD and AD were the same: 15 per 100,000 (8.4 to 27.0) in the 45- to 64-year-old population. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3). It is possible case ascertainment methods resulted in a relative underrepresentation of some forms of dementia. CONCLUSIONS: Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.

Age of Onset↗
PubMed2001

Insulin-regulated trafficking of dual-labeled glucose transporter 4 in primary rat adipose cells.

In isolated rat adipose cells, physiologically relevant insulin target cells, glucose transporter 4 (GLUT4) subcellular trafficking can be assessed by transfection of exofacially HA-tagged GLUT4. To simultaneously visualize the transfected GLUT4, we fused GFP with HA-GLUT4. With the resulting chimeras, GFP-HA-GLUT4 and HA-GLUT4-GFP, we were able to visualize for the first time the cell-surface localization, total expression, and intracellular distribution of GLUT4 in a single cell. Confocal microscopy reveals that the intracellular proportions of both GFP-HA-GLUT4 and HA-GLUT4-GFP are properly targeted to the insulin-responsive aminopeptidase-positive vesicles. Dynamic studies demonstrate close similarities in the trafficking kinetics between the two constructs and with native GLUT4. However, while the basal subcellular distribution of HA-GLUT4-GFP and the response to insulin are indistinguishable from those of HA-GLUT4 and endogenous GLUT4, most of the GFP-HA-GLUT4 is targeted to the plasma membrane with little further insulin response. Thus, HA-GLUT4-GFP will be useful to study GLUT4 trafficking in vivo while GFP on the N-terminus interferes with intracellular retention.

Adipose Tissue↗
PubMed2001

Microsatellite analysis of the inbreeding grass weed Barren Brome (Anisantha sterilis) reveals genetic diversity at the within- and between-farm scales.

Nine microsatellites were used to screen 131 samples of Barren Brome (Anisantha sterilis: synonym Bromus sterilis) collected from within the fields of three English farms [from Oxfordshire (Oxon), Leicestershire (Leics) and Wiltshire (Wilts)] and eight seeds taken from samples of each of 10 farms across England, UK. Most individuals (approximately 97%) were homozygous. Polymorphism occurred at all nine loci in all three farms sampled at the field scale, and at most loci for nine of the other 10 farm samples. Between three and 11 alleles were found per locus. Gene diversity (D = 1 - summation operator p(i)2) ranged from 0.088 to 0.760. Polymorphism occurred among individuals within and among fields, and farms. Some alleles were found in only one farm. On the basis of the alleles at all nine loci in the 211 sampled plants, a total of 92 (44%) different genotypes was identified. Clustering analysis using the unweighted pair group method with arithmetic averages (UPGMA) for the combined Oxon, Wilts and Leics samples did not cluster them into their respective farms. Similarly, a phenogram of samples from all 10 farms showed considerable mixing of individuals with respect to farm origins. Identification of genotypes on field plans showed evidence of both spatial localization and mixing. Previous reports have suggested that A. sterilis is strictly inbreeding with little intrapopulation variation at the genetic level. Our data reveal that A. sterilis exists as numerous separate and genetically different lines, which are maintained by inbreeding but which very occasionally outcross. Possible explanations for this pattern of high genetic diversity are discussed.

Alleles↗
PubMed2001

Interpretation of variation across marker loci as evidence of selection.

Population structure and history have similar effects on the genetic diversity at all neutral loci. However, some marker loci may also have been strongly influenced by natural selection. Selection shapes genetic diversity in a locus-specific manner. If we could identify those loci that have responded to selection during the divergence of populations, then we may obtain better estimates of the parameters of population history by excluding these loci. Previous attempts were made to identify outlier loci from the distribution of sample statistics under neutral models of population structure and history. Unfortunately these methods depend on assumptions about population structure and history that usually cannot be verified. In this article, we define new population-specific parameters of population divergence and construct sample statistics that are estimators of these parameters. We then use the joint distribution of these estimators to identify outlier loci that may be subject to selection. We found that outlier loci are easier to recognize when this joint distribution is conditioned on the total number of allelic states represented in the pooled sample at each locus. This is so because the conditional distribution is less sensitive to the values of nuisance parameters.

Animals↗
PubMed2000

Higher-order glass-transition singularities in colloidal systems with attractive interactions.

The transition from a liquid to a glass in colloidal suspensions of particles interacting through a hard core plus an attractive square-well potential is studied within the mode-coupling-theory framework. When the width of the attractive potential is much shorter than the hard-core diameter, a reentrant behavior of the liquid-glass line and a glass-glass-transition line are found in the temperature-density plane of the model. For small well-width values, the glass-glass-transition line terminates in a third-order bifurcation point, i.e., in a A3 (cusp) singularity. On increasing the square-well width, the glass-glass line disappears, giving rise to a fourth-order A4 (swallow-tail) singularity at a critical well width. Close to the A3 and A4 singularities the decay of the density correlators shows stretching of huge dynamical windows, in particular logarithmic time dependence.

Journal Article↗
PubMed2000

Early exclusion of hand1-deficient cells from distinct regions of the left ventricular myocardium in chimeric mouse embryos.

The basic helix-loop-helix transcription factor gene Hand1 has been implicated in development of the heart. However, the early lethality of Hand1-null mutant mouse embryos has precluded a precise understanding of its function. In this study, we have generated Hand1 homozygous mutant ES cells and performed in vitro differentiation experiments and chimeric analysis to study the role of Hand1 function during cardiac development. Hand1-null ES cells were able to differentiate into beating cardiomyocytes in vitro that expressed cardiac myosin and several cardiac-specific transcripts including Nkx2-5, alpha-cardiac actin, and the myofilament genes myosin light chain 2a and 2v. In chimeras derived from Hand1-null ES cells and ROSA26 embryos, mutant cells were underrepresented in the left caudal region of the linear heart tube at E8.0. By E9.5, after cardiac looping, mutant cells were underrepresented in the anterior region of the outer curvature of the left ventricular myocardium, but did contribute to other parts of the left ventricle and to other cardiac chambers. These results imply that Hand1 is not essential for differentiation of ventricular cardiomyocytes. Hand1-null cells were also underrepresented in several other regions of later embryos, including the rhombencephalic neural tube that was associated with a deficiency of mutant cells in the neural crest cell-derived cardiac outflow tract and first branchial arch. In summary, Hand1 has cell-autonomous functions during cardiac morphogenesis in both mesodermal and neural crest derivatives.

Animals↗
PubMed2000

Initial clinical experience with ambulatory use of an implantable atrial defibrillator for conversion of atrial fibrillation. Metrix Investigators.

BACKGROUND: A recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. METHODS AND RESULTS: An atrial defibrillator was implanted in 105 patients (75 men; mean age, 59+/-12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented "not at all," 10 represented "extremely") after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6+/-1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2+/-2.4 for successful therapy and 4.2+/-2.2 for unsuccessful therapy (P:>0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4+/-3. 3 versus 8.7+/-1.3, P:<0.05). There was no ventricular proarrhythmia observed throughout the course of this study. CONCLUSIONS: Ambulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Adult↗
PubMed2000

The glial cells missing-1 protein is essential for branching morphogenesis in the chorioallantoic placenta.

Trophoblast cells of the placenta are established at the blastocyst stage and differentiate into specialized subtypes after implantation. In mice, the outer layer of the placenta consists of trophoblast giant cells that invade the uterus and promote maternal blood flow to the implantation site by producing cytokines with angiogenic and vasodilatory actions. The innermost layer, called the labyrinth, consists of branched villi that provide a large surface area for nutrient transport and are composed of trophoblast cells and underlying mesodermal cells derived from the allantois. The chorioallantoic villi develop after embryonic day (E) 8.5 through extensive folding and branching of an initially flat sheet of trophoblast cells, the chorionic plate, in response to contact with the allantois. We show here that Gcm1, encoding the transcription factor glial cells missing-1 (Gcm1), is expressed in small clusters of chorionic trophoblast cells at the flat chorionic plate stage and at sites of chorioallantoic folding and extension when morphogenesis begins. Mutation of Gcm1 in mice causes a complete block to branching of the chorioallantoic interface, resulting in embryonic mortality by E10 due to the absence of the placental labyrinth. In addition, chorionic trophoblast cells in Gcm1-deficient placentas do not fuse to form syncytiotrophoblast. Abnormal development of placental villi is frequently associated with fetal death and intrauterine growth restriction in humans, and our studies provide the earliest molecular insight into this aspect of placental development.

Animals↗
PubMed2000

Hypernatraemia in early infancy.

Hypernatraemia, defined as serum sodium > 150 mmol/l, is still seen frequently in tropical environments. We describe two infants, one with poor fluid intake and excessive wrapping and the other with a high solute intake, both of whom presented in a state of severe hypernatraemia. The pathophysiology of this condition is outlined, as are the major causes, such as sodium overload, inadequate water intake, increased water loss of non-renal origin, increased water loss of renal origin and essential hypernatraemia. The literature is reviewed and the current basis for management is appraised and discussed.

Dehydration↗
PubMed2000

Abnormal patterns of breathing during swallowing in neurological disorders.

Swallowing momentarily inhibits breathing, and normally the great majority of apnoeas which accompany a swallow are followed by expiration (xE swallows). This swallowing-breathing interaction is regarded as one of several mechanisms by which the airway is protected from aspiration during swallowing. The purpose of this study was to investigate the interaction of breathing and swallowing in two groups of neurological patients. Twenty-two patients with defined neurological disorders involving various structures or pathways (brain, spinal cord and peripheral nerves) were studied to determine whether particular lesions resulted in breakdown of the normal breathing pattern (22 normal subjects were also assessed and their breathing-swallowing pattern was compared with that of neurological patients). Subsequently, 32 patients with motor neurone disease (MND) were studied to identify factors associated with an abnormal pattern (i.e. swallow apnoeas followed by inspiration) and to clarify whether an abnormal pattern is related to chest infections, episodes of coughing and choking during meals, and prognosis. The swallow apnoea in patients with brain, spinal cord and peripheral neurological diseases was followed by inspiration more frequently than expected [20/22 (91%) patients compared with 2/22 (9%) of normal subjects, P: < 0.001], but this was not associated with a specific site of lesion(s). However, patients with corticobulbar involvement tended to have post-apnoea inspiration more often than those without. MND patients commonly displayed an abnormal pattern during swallowing [14/32 (44%) patients] characterized by inspiration after swallow, prolonged swallow apnoea and multiple swallows per bolus. Over the period of follow-up (12-18 months) this pattern did not predict chest infections, coughing and choking episodes during meals or survival. It seems likely that post-swallowing apnoea inspiration is a non-specific concomitant of disordered swallowing and/or breathing rather than being an important mechanism of aspiration per se or of symptom production.

Adult↗
PubMed2000

ESHRE guidelines for good practice in IVF laboratories. Committee of the Special Interest Group on Embryology of the European Society of Human Reproduction and Embryology.

Education has always been a priority for the European Society of Human Reproduction and Embryology (ESHRE). Many efforts have been dedicated to promoting knowledge of techniques, procedures and strategies in order to ensure use of the highest quality practices in reproductive medicine. The need to develop a set of guidelines was a logical consequence that found its first expression in 1990, when Focus on Reproduction (vol. 1, pp. 10-38) published the first guidelines which were distributed among the membership. Five years later a new, more complete edition with several novel techniques and developments appeared in Human Reproduction (vol. 10, pp. 1246-1271). Both have proved to be invaluable references. Five more years have now passed. The necessity to produce current guidelines for good IVF laboratory practice has provided the strongest motivation. This originated from the increasing awareness that embryologists have a duty to prevent unintentional incidents that might result from poor practice in the laboratory. Therefore, the Embryology Special Interest Group (SIG) undertook to draw up guidelines aimed at giving support and guidance to the laboratory staff. All the aspects required to provide a safe working system were taken into consideration by members of the SIG and their effort produced this document. We hope that it will assist staff in achieving the best clinical outcome for their patients.

Cryopreservation↗