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Biomedical subjects

S Cox

Publications and source records attributed to S Cox.

At least 19 recordsLinked to original sources
PubMed2002

Expression in plants and immunogenicity of plant virus-based experimental rabies vaccine.

A new approach to the production and delivery of vaccine antigens is the use of engineered amino virus-based vectors. A chimeric peptide containing antigenic determinants from rabies virus glycoprotein (G protein) (amino acids 253-275) and nucleoprotein (N protein) (amino acids 404-418) was PCR-amplified and cloned as a translational fusion product with the alfalfa mosaic virus (AlMV) coat protein (CP). This recombinant CP was expressed in two plant virus-based expression systems. The first one utilized transgenic Nicotiana tabacum cv. Samsun NN plants providing replicative functions in trans for full-length infectious RNA3 of AlMV (NF1-g24). The second one utilized Nicotiana benthamiana and spinach (Spinacia oleracea) plants using autonomously replicating tobacco mosaic virus (TMV) lacking native CP (Av/A4-g24). Recombinant virus containing the chimeric rabies virus epitope was isolated from infected transgenic N. tabacum cv. Samsun NN plants and used for parenteral immunization of mice. Mice immunized with recombinant virus were protected against challenge infection. Based on the previously demonstrated efficacy of this plant virus-based experimental rabies vaccine when orally administered to mice in virus-infected unprocessed raw spinach leaves, we assessed its efficacy in human volunteers. Three of five volunteers who had previously been immunized against rabies virus with a conventional vaccine specifically responded against the peptide antigen after ingesting spinach leaves infected with the recombinant virus. When rabies virus non-immune individuals were fed the same material, 5/9 demonstrated significant antibody responses to either rabies virus or AlMV. Following a single dose of conventional rabies virus vaccine, three of these individuals showed detectable levels of rabies virus-neutralizing antibodies, whereas none of five controls revealed these antibodies. These findings provide clear indication of the potential of the plant virus-based expression systems as supplementary oral booster for rabies vaccinations.

Administration, Oral↗
PubMed2002

Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom.

In 2001, the United Kingdom experienced its worst epidemic of foot-and-mouth disease (FMD). To date approximately 3.9 million animals have been culled and direct and indirect revenue losses are probably in excess of pound 12 billion. This study was carried out to investigate the biological characteristics of the FMD virus strain O/UKG/2001 responsible for the epidemic. Animal transmission experiments indicated that this strain is not host restricted and will infect the three main susceptible livestock species (cattle, sheep and pigs). Immunisation with high potency emergency vaccine derived from O(1) Manisa strain of FMD virus protected all three species against clinical disease when challenged with FMD virus strain O/UKG/2001.

Animals↗
PubMed2002

Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease.

OBJECTIVES: To determine whether the rehospitalisation and primary care requirements of infants with chronic lung disease (CLD) during the first two years after birth were influenced by a requirement for supplementary oxygen after discharge from the neonatal intensive care unit. METHODS: Review of records from both the hospital and general practitioner. PATIENTS: 235 infants, median gestational age 27 (range 22-31) weeks, 88 of whom were receiving supplementary oxygen when discharged home. RESULTS: Overall, the infants required a median of 2 (range 0-20) admissions per patient, 8 (0-41) outpatient attendances, 13 (0-76) contacts with the general practitioner, and 17 (0-169) consultations with other primary healthcare professionals. The home oxygen patients required significantly more and longer admissions (p < 0.01) and more outpatient attendances (p < 0.05). The total cost of care per infant of the home oxygen group was greater (p < 0.001); this reflected higher costs for hospital stay (p < 0.01), total inpatient care (p < 0.01), and primary care drugs (p < 0.01). CONCLUSION: Despite routine use of antenatal steroids and postnatal surfactant, certain patients with CLD, particularly those who receive home oxygen treatment, show high rates of utilisation of health service resources after discharge from the neonatal care unit.

Analysis of Variance↗
PubMed2002

A new scale to assess radiographic success of secondary alveolar bone grafts.

OBJECTIVES: To propose a new scale for evaluating the position of the bone graft within the cleft and assess its inter- and intraobserver reliability. DESIGN: Sixty-six patients (70 cleft sites) over a 14-year period were assessed, 90% of patients retrospectively and 10% prospectively. The radiographs were reviewed by two clinicians in controlled conditions twice, with 1 week between assessments. Both clinicians were blind to patient identity. OUTCOME MEASURES: A new scale subdividing the position of the bone into one of six categories was used. The radiographs were also assessed using the Bergland scale. RESULTS: Using the Bergland scale, 62.9% of the cleft sites were type I, 21.4% type II, 4.3% type III, and 5.7% type IV. It was not possible to assess 5.7% of the clefts with this scale because the canine was unerupted. Using the Chelsea alveolar bone graft scale, 58% were category A, 20% B, 7% C, 3% D, 3% E, and 9% F. CONCLUSIONS: The above scale can be used to determine accurately the position of bone within the cleft site. It can be used in the mixed dentition prior to eruption of the canine. It demonstrated moderate to substantial inter- and intraobserver reliability and offers several advantages, compared with other scales.

Adolescent↗
PubMed2001

Identification of selective inhibitors of cyclin dependent kinase 4.

A new structural type of kinase inhibitor, containing a benzocarbazole nucleus, has been identified. Members of the series are selective for inhibition of the cyclin dependent kinase family of enzymes. Although the cdks are highly homologous, representatives of the series showed intra-cdk selectivities, especially for cdk4. SAR studies elucidated the important features of the molecules for inhibition.

Carbazoles↗
PubMed2001

Quinazolines as cyclin dependent kinase inhibitors.

Quinazolines have been identified as inhibitors of CDK4/D1 and CDK2/E. Aspects of the SAR were investigated using solution-phase, parallel synthesis. An X-ray crystal structure was obtained of quinazoline 51 bound in CDK2 and key interactions within the ATP binding pocket are defined.

Binding, Competitive↗
PubMed2001

A cyclin D1/cyclin-dependent kinase 4 binding site within the C domain of the retinoblastoma protein.

Phosphorylation of the retinoblastoma protein (Rb) by the cyclin D1/cyclin-dependent kinase (cdk) 4 complex (cdk4/D1) is a key regulatory step for maintaining the orderly progression of the cell cycle. The B domain of Rb contains a site that recognizes and binds the LXCXE motif found in D-type cyclins. This interaction is important for phosphorylation of Rb by cdk4/D1, although in vitro the Rb C domain alone is efficiently phosphorylated by cdk4/D1. A mutation in the C domain of Rb, L901Q, has been identified that completely abolishes cdk4/D1 phosphorylation of the isolated C domain. By contrast, the L901Q mutation has no effect on phosphorylation by either cyclin E/cdk2 or cyclin B/cdk1, suggesting that the interaction between L901Q and cdk4/D1 is specific. Introduction of the L901Q mutation into Rb containing the A, B, and C domains results in phosphorylation becoming predominantly dependent on the LXCXE binding region. However, when the LXCXE binding region of Rb is mutated, phosphorylation becomes dependent on the L901 site within the C domain. The L901 binding site can supplant the LXCXE binding site for the cdk4/D1-dependent phosphorylation of S780 and S795 but not S807/S811. Despite the limited homology between C domains of Rb, p107, and p130, the L901 site is conserved and introduction of the L925Q mutation into the isolated C domain of p107 also inhibits phosphorylation by cdk4/D1. These data support a model for cdk4/D1 recognizing two independent binding sites in Rb and suggests a conservation of this C domain binding motif for cyclin D1/cdk4 kinase among the Rb family of proteins.

Binding Sites↗
PubMed2001

Diagnosis of heart failure in elderly patients in primary care.

BACKGROUND: Heart failure is difficult to diagnose in a primary care setting with a reported false positive diagnosis in up to 70% of cases. AIMS: To use echocardiography in a large rural practice to evaluate the accuracy of diagnosis of heart failure in patients over 65 years of age. METHODS: Sixty patients with a previous diagnosis of heart failure were selected at random from the practice records and were invited to attend for an echocardiogram at the practice premises. RESULTS: Fifty-eight patients attended, the age was 81+/-7 years, 29% had impaired left ventricular (LV) systolic function of whom 65% were in atrial fibrillation. A further 7% had isolated diastolic LV dysfunction. The prevalence of heart failure by clinical assessment was 29 per 1000 in this patient group and 9 per 1000 when echocardiography was used to confirm the diagnosis. CONCLUSION: True heart failure in this population is less prevalent than has been estimated from practice records.

Aged↗
PubMed2001

Increased numbers of caveolae in retinal endothelium and pericytes in hypertensive diabetic rats.

PURPOSE: Long-term clinical studies have now shown that tight control of blood pressure in type 2 diabetes reduces the risk of diabetes-related death and common diabetic complications, including diabetic retinopathy. However, the mechanisms by which hypertension enhances diabetic microvascular disease, especially diabetic retinopathy, are poorly understood. We developed an experimental model of hypertension in diabetic rats and studied the early ultrastructural changes in retinal capillaries under these conditions. METHODS: Hypertension was induced in diabetic BioBreeding (BB) rats by unilateral nephrectomy, weekly subcutaneous mineralocorticoid and 0.9% oral saline. Serial blood pressures and ultrastructural features of retinal capillaries were recorded in four groups: normotensive Wistar rats, normotensive diabetic rats, hypertensive Wistar rats and hypertensive diabetic rats. RESULTS: A significant and sustained increase in systolic blood pressure occurred in both groups of nephrectomised rats. There was a significant increase in the number of caveolae (i) in both pericytes and endothelial cells in animals with hypertension and diabetes together compared with all other groups and (ii) in pericytes in animals with diabetes alone. The number of direct contacts between pericytes and endothelial cells was reduced in diabetic and hypertensive diabetic animals. Hypertension and diabetes had an interactive effect in producing retinal capillary basement membrane thickening. CONCLUSIONS: In the BB rat hypertension and diabetes have an interactive effect in increasing the number of caveolae in both endothelial cells and pericytes. We speculate that this may be a reflection of changes in calcium and nitric oxide metabolism in these animals.

Animals↗
PubMed2001

A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.

Adolescent↗
PubMed2001

Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection.

AIMS: To compare the use of health care resources and associated costs between infants with chronic lung disease (CLD) who had or had not an admission with a proven respiratory syncytial virus (RSV) infection. METHODS: Review of community care, outpatient attendances, and readmissions in the first two years after birth. PATIENTS: 235 infants (median gestational age 27 weeks) evaluated in four groups: 45 infants with a proven RSV admission (RSV proven); 24 with a probable bronchiolitis admission; 60 with other respiratory admissions; and 106 with non-respiratory or no admissions. RESULTS: The RSV proven compared to the other groups required more frequent and longer admissions to general paediatric wards and intensive care units, more outpatient attendances and GP consultations for respiratory related disorders, and had a higher total cost of care. CONCLUSION: RSV hospitalisation in patients with CLD is associated with increased health service utilisation and costs in the first two years after birth.

Analysis of Variance↗
PubMed2001

The need for palliative care for patients with non-cancer diseases: a review of the evidence.

The palliative care needs of patients with cancer are understood and managed well by specialist palliative care services. Patients dying of non-cancer diseases are rarely offered these services. A literature review was conducted to determine the physical and psychosocial problems of patients dying from non-cancer diseases. Studies were identified using a systematic keyword search of six electronic databases. Fourteen studies were identified and assessed according to rigour of design. Findings suggest that some patients dying of non-cancer have needs comparable with those dying of cancer. Low response rates, subject bias, and measurement bias mean that findings should be viewed with caution. More prospective, rigorously designed research is necessary to identify which patients with non-cancer diagnoses may benefit from specialist palliative care.

Health Services Needs and Demand↗
PubMed2000

From sequence to chromosome: the tip of the X chromosome of D. melanogaster.

One of the rewards of having a Drosophila melanogaster whole-genome sequence will be the potential to understand the molecular bases for structural features of chromosomes that have been a long-standing puzzle. Analysis of 2.6 megabases of sequence from the tip of the X chromosome of Drosophila identifies 273 genes. Cloned DNAs from the characteristic bulbous structure at the tip of the X chromosome in the region of the broad complex display an unusual pattern of in situ hybridization. Sequence analysis revealed that this region comprises 154 kilobases of DNA flanked by 1.2-kilobases of inverted repeats, each composed of a 350-base pair satellite related element. Thus, some aspects of chromosome structure appear to be revealed directly within the DNA sequence itself.

Animals↗
PubMed2000

Follicular development in transplanted fetal and neonatal mouse ovaries is influenced by the gonadal status of the adult recipient.

OBJECTIVE(S): To investigate the pattern of follicular development in transplanted fetal and neonatal mouse ovaries in the presence or absence of the recipient's own ovaries. DESIGN: Controlled experiment. SETTING: Academic research laboratory, Department of Physiology, Monash University, Clayton, Australia. INTERVENTION(S): Mouse ovaries from 16-day-old fetuses, 3-day-old neonates, and 10-day-old neonates were transplanted under the kidney capsule of adult female mice, which either retained their own ovaries in situ or were bilaterally ovariectomized. MAIN OUTCOME MEASURE(S): Histologic analysis. RESULT(S): By 4 weeks after transplantation, fetal and neonatal ovaries transplanted to ovariectomized recipients displayed a pattern of follicular development similar to that observed in in situ adult mouse ovaries. In contrast, follicular development did not progress beyond the early antral stage in fetal and 3-day-old ovaries transplanted to recipients that retained their in situ ovaries. However, 10-day-old ovaries transplanted to recipients that retained their in situ ovaries displayed full follicular development and corpora lutea formation by 8 weeks after transplantation. CONCLUSION(S): Follicular development in transplanted immature ovarian tissue is influenced by the age of the donor ovary and gonadal status of the recipient. (Fertil Steril(R) 2000;74:000-00. Copyright2000 by American Society for Reproductive Medicine.)

Age Factors↗