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Biomedical subjects

C Walton

Publications and source records attributed to C Walton.

At least 19 recordsLinked to original sources
PubMed2003

Caffeine increases spinal excitability in humans.

The Hoffman reflex (H reflex) has long been established as a measure of spinal excitability. Caffeine is one of the most widely consumed drugs in the world. Because it is known to increase excitatory neurotransmission, we hypothesized that caffeine would increase spinal excitability and thus alter the H reflex by increasing its amplitude. Seven subjects each attended the laboratory on 2 days. Caffeine (6 mg/kg) was administered on one day and a placebo was administered on the other. The tibial nerve was stimulated at incremental intensities to create an H-reflex recruitment curve prior to capsule administration (pretest) and 1 h later (posttest) on each day. The slope of H-reflex recruitment curve normalized to that of the M wave (H(slp)/M(slp)) was compared (pretest to posttest). Caffeine increased spinal excitability 43 +/- 17% (P < 0.05). Thus, caffeine may be used to safely increase spinal excitability in electrophysiological studies of the human neuromuscular system. Our results also suggest that caffeine intake should be controlled when the H reflex is used in diagnostic and experimental situations.

Action Potentials↗
PubMed2001

Genetic population structure and introgression in Anopheles dirus mosquitoes in South-east Asia.

Genetic structure and species relationships were studied in three closely related mosquito species, Anopheles dirus A, C and D in Thailand using 11 microsatellite loci and compared with previous mitochondrial DNA (mtDNA) data on the same populations. All three species were well differentiated from each other at the microsatellite loci. Given the almost complete absence of mtDNA differentiation between An. dirus A and D, this endorses the previous suggestion of mtDNA introgression between these species. The high degree of differentiation between the northern and southern population of An. dirus C (RST = 0.401), in agreement with mtDNA data, is suggestive of incipient species. The lack of genetic structure indicated by microsatellites in four populations of An. dirus A across northern Thailand also concurs with mtDNA data. However, in An. dirus D a limited but significant level of structure was detected by microsatellites over ~400 km in northern Thailand, whereas the mtDNA detected no population differentiation over a much larger area (>1200 km). There is prior evidence for population expansion in the mtDNA. If this is due to a selective sweep originating in An. dirus D, the microsatellite data may indicate greater barriers to gene flow within An. dirus D than in species A. Alternatively, there may have been historical introgression of mtDNA and subsequent demographic expansion which occurred first in An. dirus D so enabling it to accumulate some population differentiation. In the latter case the lack of migration-drift equilibrium precludes the inference of absolute or relative values of gene flow in An. dirus A and D.

Animals↗
PubMed2001

Transplantation of human hepatocytes into tolerized genetically immunocompetent rats.

AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.

Albumins↗
PubMed2001

Maximizing the success rate of minimal model insulin sensitivity measurement in humans: the importance of basal glucose levels.

Minimal model analysis of glucose and insulin concentrations in the intravenous glucose tolerance test (IVGTT) has been widely used to obtain a measure of insulin sensitivity in humans. Issues of model validity and IVGTT protocol have been explored extensively. Less attention has been paid, however, to the computer programming protocol for estimating the model parameters (programming implementation). Minimal model analysis of data from an IVGTT protocol involving a high glucose dose (0.5 g/kg) and a reduced sample schedule, employed in healthy pre- or post-menopausal women, healthy men or men with coronary heart disease or chronic heart failure (20 in each group), was undertaken according to 12 different programming implementations using a commercially available model-equation-solving program. The ability of the program to arrive at an acceptable solution to the model equations gave a success rate of between 39% and 96%, depending on the implementation. Variation in basal glucose assignment significantly affected the magnitude of estimates of insulin sensitivity. The maximum modelling success rate was achieved by introduction of an imputed glucose measurement at 360 min from the glucose injection, taking the basal glucose level as the fasting glucose concentration, and overweighting the initial glucose measurement after a delay for mixing. Use of this implementation to analyse data from a study comparing insulin sensitivities obtained using the minimal model and a euglycaemic clamp reference gave a correlation of 0.80 (P<0.001) between the two methods. Straightforward variations in programming implementation, involving appropriate assignment of the basal glucose concentration and use of an imputed glucose measurement signifying re-establishment of basal glucose levels following the IVGTT, can considerably improve modelling success rate.

Analysis of Variance↗
PubMed2001

Liver cell transplantation -- novel animal model for human hepatic viral infections.

AIM: To generate a model of human hepatitis B infection (HBV) in immunocompetent rats with chimeric human liver. METHODS AND RESULTS: Normal rats were tolerized to human hepatocytes by exposure to human hepatocytes at day 17 of gestation. We transplanted human hepatocytes and inoculated HBV into the rats after birth. Mixed lymphocytes assay, a measure for tolerance, indicated that animals fetally exposed to human hepatocytes developed tolerance to human hepatocytes. Spleen lymphocytes from tolerized animals did not proliferate when challenged with donor human hepatocytes. In contrast, control animals given saline fetally developed no tolerance to human hepatocytes. Tolerant animals with transplanted human hepatocytes were susceptible to HBV infection. Western blot analysis and immuno-histochemistry of liver sections from tolerized, HBV infected animals with transplanted human hepatocytes showed the presence of functioning human hepatocytes that synthesized human albumin, of which 30% were also positive for HB surface antigen and HBV DNA. The presence of covalent closed circular HBV DNA in the liver indicated active HBV viral replication. CONCLUSION: Tolerized rats with chimeric human livers can be infected with HBV and used as an animal model for HBV infection. Tolerized rats with chimeric human livers can also be used for generating models of other human hepatic viral diseases.

Animals↗
PubMed2001

Evidence for a new sibling species of Anopheles minimus from the Ryukyu Archipelago, Japan.

The Anopheles minimus complex is known to comprise at least 2 sibling species (A and C) in Thailand and Vietnam. This study investigated the specific status of An. minimus on Ishigaki Island, the Ryukyu Archipelago, Japan using morphological and genetic analyses. Morphological studies revealed that almost all (99.5%) of the adult mosquitoes are characterized by the humeral pale spot on the costa of their wings, a character that partially differentiates species A and C elsewhere. A high frequency (81.4%) have a pale fringe spot at the tip of vein 1A, a character rarely observed in other An. minimus populations. Significant seasonal variation in the size of wild An. minimus mosquitoes on the island was observed, with the largest size in the winter. Scanning micrographs of the cibarial armature of females from Ishigaki Island revealed that over 90% had cone filaments clearly differing in shape from those of species A or C. The Giemsa-stained metaphase karyotypes of larval brain cells were somewhat similar to those of species A, with a few exceptions, but were very different from those reported for species C. Crossing experiments between species A (CM strain) from Thailand and the progeny of An. minimus from Ishigaki Island (ISG strain) revealed postzygotic genetic incompatibility, although no prezygotic isolation. Hybrid progeny were only obtained from CM female x ISG male. F2 hybrid progeny were not obtained, since the hybrid males were sterile or almost sterile with atrophied testes or abnormal spermatozoa, although the polytene chromosomes of hybrid larvae showed synapsis. The hybrid females backcrossed with either CM or ISG males laid eggs with significantly lowered fertility and viability. The sequence for the D3 region of the 28S gene of ribosomal DNA of the ISG strain differed from those of species A and C. In addition, sequence data from Vietnamese mosquitoes suggest that the An. minimus complex may contain additional species. The morphological, cytogenetic, molecular, and hybridization evidence together suggest the existence of another sibling species of the An. minimus complex on Ishigaki Island, which is provisionally designated An. minimus species E.

Animals↗
PubMed2000

Population structure and population history of Anopheles dirus mosquitoes in Southeast Asia.

Separating the confounding effects of long-term population history from gene flow can be difficult. Here, we address the question of what inferences about gene flow can be made from mitochondrial sequence data in three closely related species of mosquitoes, Anopheles dirus species A, C, and D, from southeast Asia. A total of 84 sequences of 923 bp of the mitochondrial cytochrome oxidase I gene were obtained from 14 populations in Thailand, Myanmar, and Bangladesh. The genealogy of sequences obtained from two populations of AN: dirus C indicates no contemporary gene flow between them. The F(ST) value of 0.421 therefore probably represents a recent common history, perhaps involving colonization events. Anopheles dirus A and D are parapatric, yet no differentiation was seen either within or between species. The starlike genealogy of their haplotypes, smooth unimodal mismatch distributions, and excess of low frequency mutations indicate population expansion in An. dirus A and D. This, rather than widespread gene flow, explains their low within-species F(ST) values (0.018 and 0.022). The greater genetic diversity of An. dirus D suggests that expansion occurred first in species D and subsequently in species A. The current geographical separation and low hybrid fitness of these species also argue against ongoing interspecific gene flow. They suggest instead either historical introgression of mtDNA from An. dirus D into species A followed by independent range expansions, or a selective sweep of mtDNA that originated in An. dirus D. While not excluding contemporary gene flow, historical population processes are sufficient to explain the data in An. dirus A and D. The genealogical relationships between haplotypes could not be used to make inferences of gene flow because of extensive homoplasy due to hypervariable sites and possibly also recombination. However, it is concluded that this approach, rather than the use of fixation indices, is required in the future to understand contemporary gene flow in these mosquitoes. The implications of these results for understanding gene flow in another important and comparable group of malaria vector mosquitoes in Africa, the An. gambiae complex, are also discussed.

Animals↗
PubMed1999

Identification of five species of the Anopheles dirus complex from Thailand, using allele-specific polymerase chain reaction.

The Anopheles dirus complex of mosquitoes contains some of the most important vectors of malaria in Southeast Asia. To distinguish five species of the complex that occur in Thailand, a method using the polymerase chain reaction (PCR) was developed. The method utilizes allele-specific amplification to detect fixed differences between the species in the DNA sequence of the ribosomal DNA internal transcribed spacer 2. Primers were designed to amplify fragments of diagnostic length from the DNA of the different species. The method was tested on 179 mosquitoes of the An. dirus complex from many parts of Thailand and shown to be effective. Every specimen was unambiguously identified as species A, B, C, D or F (i.e. An. dirus s.s. species B, C, D or An. nemophilous, respectively) by the PCR method, with confirmation of 58/61 identifications from polytene chromosome characteristics. For the other three specimens (3/44 from Kanchanaburi 5 locality), there was disagreement between the PCR and chromosomal methods of species identification (probably due to errors in the chromosomal identifications). Primers can be combined in a single PCR reaction providing a rapid, sensitive and straightforward method of species identification. Only small quantities of DNA are required, leaving most of the mosquito to be used for other analyses.

Alleles↗
PubMed1999

Surveillance of occupational and work-related diseases between 1993 and 1996 in an engineering company.

There are established reporting schemes for some occupational and work-related illnesses but these schemes may underestimate the true incidence of such diseases. Not all cases may be referred to a participating physician and access to adequate diagnostic facilities are not always available. Collecting data directly from occupational health departments may overcome some problems related to under-reporting as they have good access to the entire working population within their company. The aim of this paper is to report the results from such a reporting scheme operated by a large multi-national engineering company during the period 1993-96. All UK sites of Lucas Industries (later LucasVarity) participated. A report form was completed by the occupational health department of each participating site each month. The report form gave abbreviated details of each case of occupational and work-related disease occurring at that site during the previous month. Forms were posted to a central office where the data was collated and analyzed. The incidence of respiratory diseases was broadly similar or slightly higher to that reported from other schemes. Musculoskeletal diseases were by far the most common category of disease reported. During a four year period of reporting the incidence of occupational and work-related diseases decreased overall by approximately 75%. As the reported incidence of respiratory disease was comparable with or slightly higher than that from other schemes, it appears that reporting schemes such as this can provide useful and accurate data. Musculoskeletal diseases are the most common type of disease attributed to work and should probably receive greater attention. The decrease in incidence seen in LucasVarity over time may reflect increased emphasis given to health and safety issues within the company during the reporting period.

Data Collection↗
PubMed1999

Cushing's disease masking coincidental steroid-responsive diseases.

Two cases of Cushing's disease are presented. In both cases successful treatment was followed by the development of a steroid-responsive disease condition, a seronegative arthritis in the first case and retinal vasculitis in the second. It is likely that both these conditions were unmasked by the fall in the endogenous steroid levels following the successful treatment of the Cushing's disease by trans-sphenoidal hypophysectomy.

Adrenocorticotropic Hormone↗
PubMed1999

Providing worksite health promotion through university-community partnerships. The South Carolina DOT project.

The occupational health nurse for the South Carolina Department of Transportation (SCDOT) collaborated with the Schools of Nursing within the state universities of South Carolina to coordinate individual health screenings for the employees of SCDOT. Personal Wellness Profiles (PWP) by Wellsource, Inc., were used to perform the health screenings and included family and personal histories, and assessment of blood pressure, vision, height, weight, total and high density lipoprotein cholesterol, and blood glucose levels. In addition, hepatitis and tetanus/diphtheria immunizations and influenza vaccines were provided. Each of the 48 county sites was visited twice during the semester by nursing faculty and nursing and public health students. The first visit was to collect assessment data for screening and provide immunizations. The second visit was to provide individualized analyzed data and health counseling. Of the 5,118 SCDOT employees, 3,141 were screened the first year and 2,315 were screened the second year. Of the original 3,141, only 1,549 elected to participate in the rescreening. Although the average population age was 41, 78.3% were rated at high coronary risk because of high blood pressure, high cholesterol and blood sugar levels, excessive weight and stress levels, and sedentary lifestyles.

Adult↗
PubMed1998

Crystal structures of MS2 coat protein mutants in complex with wild-type RNA operator fragments.

In MS2 assembly of phage particles results from an interaction between a coat protein dimer and a stem-loop of the RNA genome (the operator hairpin). Amino acid residues Thr45, which is universally conserved among the small RNA phages, and Thr59 are part of the specific RNA binding pocket and interact directly with the RNA; the former through a hydrogen bond, the latter through hydrophobic contacts. The crystal structures of MS2 protein capsids formed by mutants Thr45Ala and Thr59Ser, both with and without the 19 nt wild-type operator hairpin bound, are reported here. The RNA hairpin binds to these mutants in a similar way to its binding to wild-type protein. In a companion paper both mutants are shown to be deficient in RNA binding in an in vivo assay, but in vitro the equilibrium dissociation constant is significantly higher than wild-type for the Thr45Ala mutant. The change in binding affinity of the Thr45Ala mutant is probably a direct consequence of removal of direct hydrogen bonds between the protein and the RNA. The properties of the Thr59Ser mutant are more difficult to explain, but are consistent with a loss of non-polar contact.

Base Sequence↗
PubMed1998

Survey of diabetic retinopathy screening services in England and Wales.

A postal survey of diabetologists was conducted regarding the provision of diabetic retinopathy screening services in England and Wales. About 2.5 million people had no existing or planned screening service. For the rest, the perceived percentage of patients with diabetes screened varied from less than 25% to more than 90%. Multiple modes of screening were used in most units. Lack of funding was identified as the major reason for non-provision of an adequate screening service. About 18% of the units had to use research or charitable funds for screening. Only 50% of the units using optometrists for screening had standard protocols for referral. The average wait before an ophthalmologist's opinion on sight threatening retinopathy detected by screening was unacceptably high in some units. We would suggest that establishment of identical screening protocols and provision of adequate funding on a national basis ought to be the priority if incidence of blindness from diabetic retinopathy is to be reduced according to the St Vincent Declaration.

Diabetic Retinopathy↗
PubMed1998

The effect of menopause on serum uric acid levels in non-obese healthy women.

Elevated circulating serum uric acid concentrations may be linked with an increased risk of coronary heart disease (CHD). We measured serum uric acid levels in 50 premenopausal and 88 postmenopausal non-obese white women who underwent an intravenous glucose tolerance test. The uric acid concentration was significantly higher in postmenopausal versus premenopausal women. Adjustment of the data to take into account a number of confounding variables, including the age and body mass index (BMI), revealed a highly significant independent difference between the groups. BMI was found to be a significant independent predictor of the uric acid concentration, but this was confined to premenopausal women. Postmenopausal women were found to be more insulin-resistant, and significant correlations were observed between components of the insulin resistance syndrome and uric acid in both groups. We conclude that increases in serum acid in postmenopausal women may result from changes in metabolism as a consequence of the menopause, and may be associated with the increased risk of CHD seen in these women.

Adult↗
PubMed1998

MR imaging and CT of orbital infections and complications in acute rhinosinusitis.

The acute onset of orbital and periorbital inflammation presents the clinician with a diagnostic and therapeutic dilemma, the consequence of which may be very serious. The progression from the initial stage of cellulitis to orbital abscess, cavernous sinus thrombosis, brain abscess, meningitis, or visual loss may be quite rapid at times. CT, ultrasonography, and MR imaging play an important role in clinical management of these patients. Indeed, it is the information obtained through orbital imaging that directs the clinician to use the correct therapeutic modality.

Abscess↗
PubMed1998

Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study (HDDRISC-1).

OBJECTIVES: To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men. DESIGN: Cohort study with baseline characterisation, clinical follow-up, and identification of predictors of coronary artery disease and diabetes. SETTING: University hospital metabolic day ward. SUBJECTS: Participants in a company health programme (n=742). MAIN OUTCOME MEASURES: Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT). RESULTS: Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake. CONCLUSIONS: Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol consumption was associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.

Adult↗