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L Lawton

Publications and source records attributed to L Lawton.

12 recordsLinked to original sources

A high-resolution annotated physical map of the human chromosome 13q12-13 region containing the breast cancer susceptibility locus BRCA2.

Various types of physical mapping data were assembled by developing a set of computer programs (Integrated Mapping Package) to derive a detailed, annotated map of a 4-Mb region of human chromosome 13 that includes the BRCA2 locus. The final assembly consists of a yeast artificial chromosome (YAC) contig with 42 members spanning the 13q12-13 region and aligned contigs of 399 cosmids established by cross-hybridization between the cosmids, which were selected from a chromosome 13-specific cosmid library using inter-Alu PCR probes from the YACs. The end sequences of 60 cosmids spaced nearly evenly across the map were used to generate sequence-tagged sites (STSs), which were mapped to the YACs by PCR. A contig framework was generated by STS content mapping, and the map was assembled on this scaffold. Additional annotation was provided by 72 expressed sequences and 10 genetic markers that were positioned on the map by hybridization to cosmids.

BRCA2 Protein

Identification and characterization of three genes and two pseudogenes on chromosome 13.

A study was conducted on the feasibility of isolating genes and pseudogenes that map to chromosome 13 by a hybridization-based approach using a 13-specific library and pools of repeat-free cDNA clones. Five pairs of cDNA and chromosome 13 genomic clones were identified and characterized. Partial or full-length sequence was derived from all cDNAs, and database searches were performed for putative gene identification. Partial sequence was also obtained from the chromosome 13 genomic clones for comparison with those of the hybridizing cDNAs. As a result of these analyses we identified three genes, a putative homologue of a porcine mRNA encoding an unidentified hepatic protein, a putative homologue of a yeast integral membrane protein, and a gene for a translationally controlled tumor protein, and two processed pseudogenes, ribosomal proteins L23a and S3a. The latter was formerly identified as the v-fos transformation effector gene, Fte-1, and recently cited as a possible candidate for the BRCA2 gene on chromosome 13. All genes and pseudogenes were localized to cytogenetic bands by in situ hybridization of metaphase chromosomes with probes derived from the chromosome 13 genomic clones.

Amino Acid Sequence

Paediatric trauma--the care of Anthony.

Trauma causes more than 50% of the deaths in children under the age of 16 years. The leading cause is road traffic accidents with children being involved as passengers, pedestrians or bicycle riders (Brown et al 1993). When a paediatric trauma patient arrives in the Accident and Emergency department it is usually met with trepidation and anxiety. The care of the paediatric trauma victim follows the same protocols and procedures as with an adult. The primary survey consists of airway with cervical spine control, breathing, circulation with haemorrhage control, disability and exposure. The secondary survey consists of a head-to-toe examination. There are certain differences between children and adults, and children should never be considered as little adults. This article covers the primary survey and highlights the essential differences between adult and paediatric trauma care.

Adult

Construction and characterization of a normalized cDNA library.

We have developed a simple procedure based on reassociation kinetics that can reduce effectively the high variation in abundance among the clones of a cDNA library that represent individual mRNA species. For this normalization, we used as a model system a library of human infant brain cDNAs that were cloned directionally into a phagemid vector and, thus, could be easily converted into single-stranded circles. After controlled primer extension to synthesize a short complementary strand on each circular template, melting and reannealing of the partial duplexes at relatively low C0t, and hydroxyapatite column chromatography, unreassociated circles were recovered from the flow through fraction and electroporated into bacteria, to propagate a normalized library without a requirement for subcloning steps. An evaluation of the extent of normalization has indicated that, from an extreme range of abundance of 4 orders of magnitude in the original library, the frequency of occurrence of any clone examined in the normalized library was brought within the narrow range of only 1 order of magnitude.

Base Sequence

Clinical benchmarking improves clinical paths: experience with coronary artery bypass grafting.

BACKGROUND: Clinical paths and clinical benchmarking are consistent with, and readily adaptable to, any health care organization that espouses the principles of continuous quality improvement. CLINICAL PATHWAY: In its initial clinical path project, Borgess Medical Center analyzed and streamlined the processes of caring for a coronary artery bypass graft (CABG) patient. Team discussions were driven by comparative data, specialty guidelines, peer review organization guidelines, patient financial statements, patient records, and the applicable literature. One year after the CABG clinical paths were implemented, average total charges to the patient dropped from $35,700 to $32,700. Average length of stay also dropped, from 11.1 to 9.7 days. The mortality rate held stable at 2.7%. CLINICAL BENCHMARKING: Recognizing the opportunity to further improve its CABG clinical path, Borgess participated in MediQual's CABG benchmarking project. The team followed MediQual's five phases of clinical benchmarking: focus and opportunity assessment, outcome analysis and comparison, clinical process documentation, benchmark process comparison, and action planning, implementation, and monitoring. Using benchmark data provided by MediQual, the CABG benchmark team focused on the high-risk population and identified further opportunities for streamlining the CABG clinical pathway. Several areas for improvement were identified by comparing Borgess's practices to the benchmark hospitals. CONCLUSION: Developing a clinical path before beginning to benchmark "forced" Borgess Medical Center to develop a clear understanding of its own processes. This allowed the benchmark team to easily identify variances between its CABG processes and those of the benchmark hospitals and to select which variations the hospital should adopt.

Clinical Protocols

Selection of cDNAs using chromosome-specific genomic clones: application to human chromosome 13.

We have developed a general method for en masse isolation of cDNAs present in a normalized library by hybridization to arrayed chromosome-specific phage lambda clones; we have used this approach to initiate exon-mapping of human chromosome 13. An advantage of the simultaneous isolation of cDNA/lambda pairs is that it allows cytogenetic assignment of a bona fide genomic clone by in situ hybridization, which also verifies that the corresponding cDNA or a homologous expressed sequence resides on chromosome 13. This information is enriched by partial sequencing of a selected cDNA from both ends. The sequence of the 3' noncoding region provides an 'identifier' that is used to develop STSs, while the sequence from the 5' end, often corresponding to a coding region, is used for homology searches in databases that occasionally reveal gene functions.

Amino Acid Sequence

An investigation of the relationship between microbial and particulate indoor air pollution and the sick building syndrome.

The sick building syndrome has been the subject of research for approximately 10 years. Although it is often suggested that symptoms in office workers are due to circulating micro-organisms or particles, epidemiological studies investigating the relationship between them have been lacking. This cross-sectional study has combined medical and aerobiological assessments of offices in Great Britain and has found that, although airborne particulates and micro-organisms are unlikely to be the sole cause of the sick building syndrome, positive associations between symptom prevalence rates and levels of airborne viable bacteria and fungi within groups of buildings with similar ventilation systems, suggest a possible causal link that should be explored.

Air Microbiology

Disability, residential mobility, and changes in living arrangements.

The extent of mobility and changes in living arrangements associated with disability were studied using data from the 1984-86 Longitudinal Study of Aging. It was hypothesized that persons with significant limitations in their ability to perform normal daily activities (ADLs and IADLs) in 1984 would be more likely to move, more likely to be living with others in 1986, and more likely to have entered an institution between 1984 and 1986 than those without limitations. When only those variables that were measured in 1984 were used as predictors, this turned out to be true for institutionalization and for living with others in 1986. However, among those remaining in households, residential mobility showed little relationship to disability when other variables were controlled. When the change in disability between 1984 and 1986 was added to the prediction equation, there were strong relationships between changes in disability and both residential mobility and adjustment in living arrangement, suggesting that people respond quickly to significant changes in disability. However, because we cannot be sure that the changes in disability preceded the mobility or changes in living arrangements, we cannot claim to have established a causal link between these events.

Activities of Daily Living

Subacute hematogenous osteomyelitis: are biopsy and surgery always indicated?

Forty-four consecutive cases of subacute osteomyelitis admitted at our institution over a 12-year period were retrospectively reviewed to assess the effectiveness of conservative versus surgical treatment of this condition and to determine the indications for open biopsy and surgical debridement. Twenty-four cases were treated with antibiotics only, and 20 had surgical debridement followed by antibiotics. Except for one case that received inadequate antibiotic therapy, all patients responded well to this treatment, whether conservative or surgical. At an average follow-up of 18 months, there were no recurrences. Our results also showed that with a careful radiologic assessment of these cases, most lesions showed characteristic benign radiologic features. We can therefore conclude that conservative management of cases of subacute osteomyelitis is as effective as surgical treatment. We believe that conservative treatment with antibiotics should be the first line of management in most of these cases and that open biopsy or surgical debridement or both should be reserved for cases that do not respond to antibiotics or show aggressive radiologic features.

Adolescent

The orthopaedic manifestations of Pelizaeus-Merzbacher disease in children.

Pelizaeus-Merzbacher disease (PMD) is a degenerative leukodystrophy of the central nervous system resulting in progressive spasticity and neurologic deterioration. Seitelberger (13) divided this rare disease into six types. Five patients with the type 1 and two patients with the type II form of PMD have been treated at the Children's Hospital of Eastern Ontario. Our study sought to identify the orthopaedic manifestations of PMD and to develop a common orthopaedic profile for these patients. All children with types I and II PMD developed spastic quadriparesis, truncal hypotonia, thoracolumbar scoliosis, soft-tissue contractures of the adductors and hamstrings, osteopenia, bilateral coxa valga, and associated hip dislocation.

Bone Diseases, Metabolic

Assessment variations.

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