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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 37 records · Page 2Linked to original sources
PubMed2003

Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism?

Among the phenotypes associated with Gaucher disease, the deficiency of glucocerebrosidase, are rare patients with early onset, treatment-refractory parkinsonism. Sequencing of glucocerebrosidase in 17 such patients revealed 12 different genotypes. Fourteen patients had the common "non-neuronopathic" N370S mutation, including five N370S homozygotes. While brain glucosylsphingosine levels were not elevated, Lewy bodies were seen in the four brains available for study. The shared clinical and neuropathologic findings in this subgroup suggest that the deficiency in glucocerebrosidase may contribute to a vulnerability to parkinsonism.

Adult↗
PubMed2003

Obliterative enteritis complicating graft versus host disease.

We report a 10-year-old male with Down's syndrome, who received a bone marrow transplant for acute lymphoblastic leukaemia. Subsequent acute graft-versus-host disease (GvHD) of the gut progressed to small bowel obstruction. At laparotomy, the small bowel appeared solid and contracted with no or minimal luminal patency. Although the caecum had a lumen, it was indistensible, and it was not possible to enter the terminal ileum. Histology of the obstructed bowel showed extensive necrosis of the mucosa, muscularis mucosa and submucosa of most of the small bowel wall, causing obliteration of the lumen. The changes were presumed to be related to post inflammatory atrophy. This extreme manifestation of GvHD could thus be called obliterative enteritis. Both cytomegalovirus and adenovirus were isolated from the patient. These viruses may have contributed to the severity of the intestinal GvHD.

Adenoviridae↗
PubMed2003

Visual outcomes and amblyogenic risk factors in craniosynostotic syndromes: a review of 141 cases.

AIMS: To determine the visual outcome and prevalence of amblyogenic risk factors in children with craniosynostotic syndromes. METHODS: The case notes of 141 children seen within the craniofacial unit were reviewed and information retrieved on date of birth, age at first and last examination, cycloplegic refraction at last visit, best corrected visual acuity at last visit, horizontal ocular deviation in primary position at first visit, and alphabet pattern if any. The presence of astigmatism, its magnitude, and orientation of axis were determined. RESULTS: 40.3% of patients had 1 dioptre (D) of astigmatism or greater and, of these, 64% had oblique astigmatism in at least one eye. Anisometropia of 1D or more was found in 18% of patients (age matched normals 3.5%). Horizontal strabismus was found in 70% (38% exotropia, 32% esotropia). Visual outcome results showed 39.8% of patients (45 of 113) had visual acuity of 6/12 or worse in their better eye. CONCLUSION: In the largest study to date a poor visual outcome was shown in children with Crouzon's, Pfeiffer's, Apert's, and Saethre-Chotzen syndromes (39.8% with 6/12 or worse in the better eye) together with significant prevalence of amblyogenic risk factors.

Adolescent↗
PubMed2003

Familial vestibulocerebellar disorder maps to chromosome 13q31-q33: a new nystagmus locus.

PURPOSE: To determine a gene locus for a family with a dominantly inherited vestibulocerebellar disorder characterised by early onset, but not congenital nystagmus. DESIGN: Observational and experimental study. METHODS: We carried out a phenotypic study of a unique four generation family with nystagmus. We performed genetic linkage studies including a genome wide search. RESULTS: Affected family members developed vestibulocerebellar type nystagmus in the first two years of life. A higher incidence of strabismus was noted in affected members. Haplotype construction and analysis of recombination events linked the disorder to a locus (NYS4) on chromosome 13q31-q33 with a lod score of 6.322 at theta=0 for D13S159 and narrowed the region to a 13.8 cM region between markers D13S1300 and D13S158. CONCLUSIONS: This study suggests that the early onset acquired nystagmus seen in this family is caused by a single gene defect. Identification of the gene may hold the key to understanding pathways for early eye stabilisation and strabismus.

Cerebellar Diseases↗
PubMed2003

Prevalence of sensitisation to cellulase and xylanase in bakery workers.

AIMS: To assess the prevalence of sensitisation to a range of exogenous fungal enzymes used in bakeries, and determine the relation between sensitisation and work related symptoms. METHODS: Serum samples (n = 135) from a previous cross sectional study investigating the prevalence of respiratory symptoms and sensitisation to dust components, were reanalysed for specific IgE to the mixed enzymes cellulase, hemicellulase, and xylanase. RESULTS: Eight (6%) of sera tested had detectable specific IgE to mixed enzymes (excluding fungal alpha-amylase) and 16 (12%) to fungal alpha-amylase. A significant increase (p = 0.03) in nasal symptoms was found in those workers sensitised to enzymes (including alpha-amylase and the mixed enzymes, but with or without sensitisation to wheat flour) when compared to those sensitised to wheat flour alone. Both groups had significantly greater levels of nasal symptoms in comparison to those with no evidence of sensitisation. CONCLUSIONS: The association between specific IgE to mixed enzymes, and an increased prevalence of nasal symptoms in individuals sensitised to enzymes, highlights the importance of measuring sensitisation to the full range of exogenous enzymes used in the baking industry, as well as to wheat flour.

Cellulase↗
PubMed2003

Outcomes after localized axillary node recurrence in breast cancer.

BACKGROUND: Localized axillary recurrence (LAR) is an uncommon event. It is estimated to occur in 0.5% to 3% of patients when adequate axillary surgery has been performed. Although relatively sparse data exist on the outcome of patients with LAR, in the era of sentinel node biopsy (SNB) these data may have increased relevance. This study assesses the survival outcomes in these patients. METHODS: A retrospective chart review was completed. Patient age, tumor size, pathology, receptor status, and treatment of the primary breast carcinoma were reviewed. Axillary recurrence, treatment, and overall survival data were collected. RESULTS: Fifteen patients were identified with LAR that developed at a median of 77 months after their initial dissection. At the time of treatment for their LAR, all patients had completion axillary clearance and six also had a concurrent completion mastectomy. Further adjuvant treatment was individualized. Five patients (33%) have died, including all patients (3) who developed a LAR within 2 years of their initial breast cancer presentation. Ten-year overall survival is 56%. CONCLUSION: Our experience suggests early (<24 months) LAR is indicative of a poor prognosis. With multimodal treatment, ten-year overall survival is 56%.

Adult↗
PubMed2002

Collision-induced dissociation studies of poly(vinylidene) fluoride telomers in an electrospray-ion trap mass spectrometer.

Although fluorinated polymers are widely used in different applications, they are rarely investigated by "soft ionization" techniques such as matrix-assisted laser desorption/ionization and electrospray ionization (ESI). We report here, the desorption and fragmentation of poly(vinylidene) fluoride (PVDF) telomers in an ion trap mass spectrometer coupled to an ESI source. Protonated and lithiated telomers under collision-induced dissociation resonant excitation show mainly HF losses. Fragmentation of protonated telomers can be rationalized by a double proton-transfer mechanism and that of lithiated and anionic telomers by an ion-dipole mechanism. Both mechanisms predict the formation of a stable aromatic or a linear conjugated species, respectively. For lithiated telomers, we could determine the degree of polymerization (n) from the product ion abundance in MS2 experiments. The nature of the end group plays a substantial role in orienting the fragmentation of the PVDF ions. It is interesting to note that, in MS2 experiments, Li+ and F- act as catalysts in the fragmentation of PVDF telomers. Fragmentation of the PVDF telomer backbone was not observed under any experimental conditions.

Journal Article↗
PubMed2002

Pathological and immunological changes after challenge infection with Pasteurella multocida in naive and immunized calves.

Challenge infections of calves with Pasteurella multocida were established to characterize the local inflammatory response and determine the effect of previous exposure to live bacteria on the post-challenge immune response. Experimental infections were established by intratracheal inoculation of P. multocida in both naive calves and calves that had been previously vaccinated with two subcutaneous (s.c.) injections of live bacteria. Histological, immunohistological and cytokine expression studies were performed on bronchoalveolar lavage (BAL) samples, lung parenchymal tissues and lung lymph nodes (LN). In comparison to uninfected control animals in which no lung lesions were observed, a patchy to confluent bronchopneumonia was observed following infection of naive calves, characterized by abscess formation, haemorrhage, oedema and suppurative consolidation. Cellular analysis following infection of naive animals was characterized by an influx of neutrophils in the BAL, with macrophages and dendritic cells observed in the lesion perimeter. A significant increase in the number of CD8(+) blasts expressing MHC (major histocompatibility) II was also observed in the BAL of infected calves. Decreased expression of interleukin (IL)-1 beta and increased expression of IL-8 compared to naive unchallenged controls was apparent in lung LN. In comparison, a more limited pathology was observed in vaccinated animals post-challenge, indicating partial protection conferred by the s.c. immunization with live bacteria. Studies of vaccinated animals showed the presence of bronchial-associated lymphoid tissue (BALT) in the lung tissue and an increase in the number of B-cells and CD4(+) T-cells expressing MHCII in the lung LN after challenge. In contrast to primary infection, there was no significant influx of neutrophils in the BAL. Instead, a population of newly recruited monocytes/macrophages was observed. Increased IL-2 expression and decreased IL-8 expression was observed in the LN, while IL-1 beta expression was not detected. The reduced neutrophil and increase monocyte response in the vaccinated calves may be associated with significant changes in the gamma delta T lymphocyte population in the BAL.

Animals↗
PubMed2002

Intact cell mass spectrometry (ICMS) used to type methicillin-resistant Staphylococcus aureus: media effects and inter-laboratory reproducibility.

Intact cell mass spectrometry (ICMS) rapidly analyses the surface composition of microorganisms providing rapid, discriminatory fingerprints for identification and subtyping of important nosocomial pathogens such as methicillin resistant Staphylocccus aureus (MRSA). In this study, ICMS using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI TOF/MS) was assessed for the identification and subtyping of MRSA. An intra- and inter-laboratory reproducibility study was carried out and the effects of culture media (an important source of variation for ICMS) were also studied. Several media used for the cultural identification of MRSA were examined using a panel of well-characterised staphylococcal isolates (n=26). Six MRSA isolates were analysed over a 1-month period for intra-laboratory reproducibility on the same instrument and three different culture media. Spectra were consistent for each isolate between the four experiments on the same culture medium. Individual isolates produced different spectral profiles on different culture media. Spectra from organisms grown on Columbia blood agar contained more peaks (approximately 120) compared to Columbia agar (approximately 50) and methicillin mannitol salt agar (approximately 25). All 26 staphylococcal isolates were subjected to an inter-laboratory study on two MALDI instruments. For each isolate, the overall spectral profile was the same for each of the two instruments but the baseline threshold values was adjusted due to instrument differences in detector sensitivities. Differences between certain regions of the spectra reproducibly identified isolates belonging to the two major MRSA strains (EMRSA phage group 15 and 16). These results demonstrate ICMS with appropriate media selection is a rapid and reproducible technique for identification and discrimination of MRSA.

Culture Media↗
PubMed2002

Prognosis and response to therapy in colorectal cancer.

Colorectal cancer is Europe's second biggest cancer killer. Yet despite advances in knowledge and changes in chemotherapy practice, we have not seen great strides in improved survival. Histopathological staging is at present the most accurate prognostic factor for survival and recurrence. Improvements in staging have led to the recognition of the importance of the circumferential resection margin (CRM) and how the quality of surgery influences local recurrence rates. Further refinements in staging and increasing knowledge of tumour biology will have a large contribution to play in the future.

Colorectal Neoplasms↗
PubMed2002

Tensile strength, histological and immunohistochemical observations of periodontal wound healing in the dog.

This study was designed to study wound strength at the dentine/connective tissue interface and at the bone/connective tissue interface following full thickness flap surgery. Flaps of uniform dimension were outlined in four young adult beagle dogs using a standardised double bladed knife and vertical incisions 10 mm apart, which extended 8 mm apical to the gingival margin. Bone was removed from half the sites (eight sites in each dog), giving 32 flaps replaced on dentine and 32 sites on bone. A tensile force was applied using a microprocessor force gauge at 1, 2, 3, 7, 10, 14, 21, and 28 days. Mean tensile strengths were markedly weaker for the dentine/flap interface. At 7 days the value for flaps to dentine was 1.82 N, in contrast to 5.08 N for flaps replaced on bone. Inflammatory cell counts tended to fall markedly at 3 days for both modalities, but were higher for the dentine/flap modality at all time points. Fibroblast density peaked at 7-14 days but did not vary with type of flap over the time points studied. The amounts of fibrin were greater for the dentine/flap interface at all time points but decreased for both flap types as time progressed. Collagen type V was localised to the basement membrane and blood vessels and tended to show more foci for flaps replaced on dentine. Procollagen levels showed little change over the healing interval for both flap/bone and flap/dentine interfaces. Type III collagen synthesis was at peak levels during the first week. These findings would support efforts to stabilise periodontal flaps at early time points, especially those on dentine.

Alveolar Process↗
PubMed2002

Women with spinal cord injury and the impact of aging.

OBJECTIVES: The objectives of this study were to describe what women with longstanding spinal cord injury (SCI) feel they are experiencing as they age, how they are coping and what they require in order to ensure their continued social and economic participation in society. STUDY DESIGN, METHODS AND SETTING: :A naturalistic approach was taken, incorporating three focus groups (n=10) and key informant interviews (n=19) of women with SCI ranging in age from 31 to 70 years and living in rural and urban communities in Ontario, Canada. RESULTS: The women feel isolated and sense many of their key concerns are ignored or dismissed by health care and service providers. The common physical changes and concerns were gynecological/sexual and bowel and bladder issues. Socio-emotional changes with age included impact of their age-related changes on important relationships and re-evaluation of personal priorities. They articulated worries including declining health, increasing dependency and financial stresses. Additional resources they need to age successfully include improved environmental accessibility, assistive devices, more flexible and responsive attendant and household support, access to recreation and fitness opportunities and peer and psychological support. CONCLUSIONS: Many of the issues raised by the women were consistent with the authors' previous examination of aging in men with SCI and women with disabilities. The most striking difference was their profound sense of isolation and perceptions that health care and service providers were unprepared or unwilling to address the unique issues they face as women living and now aging with SCI.

Adaptation, Psychological↗
PubMed2002

Development and validation of an average mammalian estrogen receptor-based QSAR model.

Development and evaluation of quantitative structure activity relationships (QSARs) for predicting estrogen receptor binding from chemical structure requires reliable algorithms for three-dimensional (3D) QSAR analysis and establishment of structurally diverse training sets of chemicals whose modes of action and measures of potency are well defined. One approach to selecting an appropriate training set is to minimize the biological variability in the model development, by using structurally restricted data sets. A second approach is to extend the structural diversity of chemicals at the cost of increased variability of biological assays. In this study, the second approach was used by organizing a training set of 151 chemicals with measured human alpha Estrogen Receptor (ERalpha), mouse uterine, rat uterine, and MCF7 cell Relative Binding Affinities (RBAs). The structurally augmented training set was submitted to a 3D pattern recognition analysis to derive a model for average mammalian ER binding affinity by employing the COmmon REactivity PAttern (COREPA) approach. Elucidation of this pattern required examination of the conformational flexibility of the compounds in an attempt to reveal areas in the multidimensional descriptor space, which are most populated by the conformers of the biologically active molecules and least populated by the inactive ones. The approach is not dependent upon a predetermined and specified toxicophore or an alignment of conformers to a lead compound. Reactivity patterns associated with mammalian ER binding affinity were obtained in terms of global nucleophilicity (E(HOMO)), interatomic distances between nucleophilic sites, and local nucleophilicity (charges or delocalizabilities) of those sites. Based on derived patterns, descriptor profiles were established for identifying and ranking compounds with RBA of > 150, 150-10, 10-1 and 1-0.1% relative to 17beta-estradiol. Specificity of reactivity profiles was found to increase gradually with increasing affinities associated with RBAs ranges under study. Using the results of this analysis, an exploratory expert system was developed for use in ranking relative mammalian ER binding affinity potential for large chemical data sets. The validity of the RBA predictions were confirmed by independent development and comparison with measured RBA values.

Algorithms↗
PubMed2002

Uses and limitations of quantitative structure-activity relationships (QSARs) to categorize substances on the Canadian domestic substance list as persistent and/or bioaccumulative, and inherently toxic to non-human organisms.

Under sections 73 and 74 of the revised Canadian Environmental Protection Act (CEPA 1999), Environment Canada and Health Canada must "categorize" and "screen" about 23,000 substances on the Domestic Substances List (DSL) for persistence (P), bioaccumulation (B), and inherently toxic (iT) properties. Since experimental data for P, B and iT are only available for a few DSL substances, a workshop was held to address issues associated with the use of Quantitative Structure-Activity Relationships (QSARs) to categorize these substances. This paper describes the results of an 11-12 November 1999 International Workshop sponsored by Environment Canada to discuss potential uses and limitations of QSARs to categorize DSL substances as either persistent or bioaccumulative and iT to non-human organisms and to recommend future research needed to develop methods for predicting the P, B and iT of difficult-to-model substances.

Canada↗
PubMed2002

Androgen receptor binding affinity of pesticide "active" formulation ingredients. QSAR evaluation by COREPA method.

The COREPA approach for identifying the COmmon REactivity PAttern of biologically similar chemicals was employed to upgrade the recently derived affinity pattern for high androgen receptor (AR) binding affinity. The training set consisted of 28 steroidal and nonsteroidal ligands whose AR binding affinity was determined in competitive binding assays (in terms of pKi). The interatomic distances between nucleophilic sites and their charges providing distinct and non-overlapping integral patterns for active and inactive chemicals were assumed that it was related with the endpoint, which was under study. These stereoelectronic characteristics were used to predict pKi values of pesticide "active" formulation ingredients in an attempt to identify chemicals with potential AR binding affinity.

Biological Assay↗
PubMed2002

An integrated "4-phase" approach for setting endocrine disruption screening priorities--phase I and II predictions of estrogen receptor binding affinity.

Recent legislation mandates the US Environmental Protection Agency (EPA) to develop a screening and testing program for potential endocrine disrupting chemicals (EDCs), of which xenoestrogens figure prominently. Under the legislation, a large number of chemicals will undergo various in vitro and in vivo assays for their potential estrogenicity, as well as other hormonal activities. There is a crucial need for priority setting before this strategy can be effectively implemented. Here we report an integrated computational approach to priority setting using estrogen receptor (ER) binding as an example. This approach rationally integrates different predictive computational models into a "Four-Phase" scheme so that it can effectively identify potential estrogenic EDCs based on their predicted ER relative binding affinity (RBA). The system has been validated using an in-house ER binding assay dataset for 232 chemicals that was designed to have both broad structural diversity and a wide range of binding affinities. When applied to 58,000 chemicals identified by Walker et al. as candidates for endocrine disruption screening, some 9100 chemicals were predicted to bind to ER. Of these, only 3600 were expected to bind to ER at RBA values up to 100,000-fold less than that of 17beta-estradiol. The method ruled out 83% of the chemicals as non-binders with a very low rate of false negatives. We believe that the same integrated scheme will be equally applicable to endpoints of other endocrine disrupting mechanisms, e.g. androgen receptor binding.

Biological Assay↗
PubMed2002

Cancer of the oesophagus in Africans in sub-Saharan Africa: any hopes for its control?

Oesophageal cancer, a highly lethal tumour, occurs to a variable extent in Africans in sub-Saharan African countries. In many, its incidence remains low, as in the Ivory Coast, Mali and the Gambia. However, in other African countries, the incidence rate has risen considerably, especially in city populations, as in Durban, South Africa, in Kyadondo, Uganda, and in Harare, Zimbabwe, rising to levels far higher than those reported in white populations. As to risk factors, in some African settings, smoking is a factor, and in others, alcohol consumption. Nutritionally, one enquiry, made in Durban, indicated the use of less-refined cereal products, with higher consumptions of vegetables and fruit, to be protective. In developed populations, protective factors are considered to be those characteristic of a "prudent" lifestyle. However, known risk factors largely fail to explain the high variability in the disease's occurrence. In seeking to combat the disease, it is thought unlikely that most Africans, especially urban dwellers, are willing to alter their lifestyle appropriately, even with the understanding that the changes would confer other protective benefits. This suggests that further rises, especially in the contexts of high incidence rates, are inevitable.

Africa South of the Sahara↗