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Biomedical subjects

William Walker

Publications and source records attributed to William Walker.

10 recordsLinked to original sources
PubMed2006

Assistive technology use among adolescents and young adults with spina bifida.

OBJECTIVES: We sought to determine the use of assistive technology among a population of individuals with spina bifida. METHODS: We performed a descriptive analysis of individuals aged 13 to 27 years diagnosed with myelomeningocele (n=348) using data obtained from an existing database at Children's Hospital and Regional Medical Center, Seattle, Washington. We summarized disease characteristics, utilization of assistive technology, community and self-care independence, and other variables. RESULTS: Eighty-four percent of the respondents lived with at least 1 of their natural parents. Fifty-seven percent used wheelchairs, 35% used braces, and 23% used walking aids. Independent self-care was a common skill, but 72% reported limited participation in structured activities. Half were aged 18 years or older; of those, only 50% had completed high school and 71% were unemployed. Those aged younger than 18 years were all still in school (100%). CONCLUSIONS: Adolescents and young adults with spina bifida rely on assistive technology and specialized care routines to maintain their health. Assistive technology use for mobility is common; little is known about secondary complications associated with use of these technologies or the use of assistive technology to address learning disabilities and other societal barriers. Underutilization of assistive technology could delay successful transitions to independent living and community participation.

Activities of Daily Living↗
PubMed2006

Developing a VATS lobectomy programme--can VATS lobectomy be taught?

OBJECTIVE: Although VATS lobectomy has been demonstrated to be safe and effective, the technique is not widely practiced. This may, in part, reflect difficulty in acquiring appropriate skills. We have evaluated the effect of experience and training on surgical outcomes during the development and establishment of a VATS lobectomy programme. METHODS: Data were collected prospectively on 276 consecutive VATS lobectomies under the care of a single consultant as either the primary surgeon or supervising four trainees. The series was divided into cohorts of 46 patients. These comprised one trainee cohort and five sequential consultant cohorts. Statistical analysis utilised standard tests of significance. RESULTS: Increasing experience with the VATS lobectomy programme was associated with a significant reduction in operating time but intraoperative blood loss and postoperative stay were not influenced by increasing consultant surgical experience. Training was associated with a mean increase of 22 min operative time (p=0.0005) but no increase in intraoperative blood loss, morbidity, mortality or postoperative stay. The 46 trainee operative times were similar to the first 46 consultant cases. CONCLUSIONS: VATS lobectomy can be safely taught to trainee thoracic surgeons. However, in view of the limited number of centres undertaking VATS lobectomy, training should be coordinated at a national level to concentrate experience and improve uptake of this technique.

Blood Loss, Surgical↗
PubMed2005

Mnt-Max to Myc-Max complex switching regulates cell cycle entry.

The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and is an important regulator of cell cycle entry. In contrast to c-Myc, the putative Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt and Myc require interaction with Max for specific DNA binding at E-box sites, but have opposing transcriptional activities. Here, we show that c-Myc induction during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes. Mnt overexpression suppressed cell cycle entry and cell proliferation, suggesting that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry. Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse embryo fibroblasts rescued the cell cycle entry and proliferative block caused by c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a fundamental role in regulating cell cycle entry and proliferation.

Animals↗
PubMed2004

Identification, characterization, and functional analysis of sp1 transcript variants expressed in germ cells during mouse spermatogenesis.

The SP family of zinc-finger transcription factors are important mediators of selective gene activation during embryonic development and cellular differentiation. SP-binding GC-box domains are common cis-regulatory elements present in the promoters of several genes expressed in a developmentally specific manner in differentiating mouse germ cells. Four Sp1 cDNAs were isolated from a mouse pachytene spermatocyte cDNA library and characterized by DNA sequence analysis. Northern blot studies revealed that these cDNAs corresponded to 3 full-length Sp1 transcripts (4.1, 3.7, and 3.2 kilobases [kb]) and an additional 1.4-kb 5'-truncated Sp1 transcript that are temporally expressed during spermatogenesis. Quantitative real-time polymerase chain reaction studies verified that the highest levels of Sp1 transcript expression of 4.1, 3.7, and 3.2 kb occur in the primary spermatocytes. The spatial and temporal expression patterns of these Sp1 transcripts and their encoded 60-kDa and 90-kDa SP1 proteins were demonstrated using in situ hybridization and immunohistochemical analyses. To assess the transcriptional properties of these SP1 transcription factors, SP-deficient Drosophila SL2 cells were stably transfected with the respective Sp1 cDNA expression vectors and cotransfected with either Ldh2, Ldh3, or Creb promoter/luciferase reporter constructs. The levels of SP-mediated luciferase expression observed depended on the structure of the glutamine-rich transactivation domains and the number of GC-box elements present in the respective promoters. The alterations observed in germ cells in the patterns of expression of the Sp1 transcripts encoding the 60-kDa and 90-kDa SP1 isoforms suggest that these SP1 factors may be involved in mediating stage-specific and cell type-specific gene expression during mouse spermatogenesis.

Animals↗
PubMed2004

Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition.

The majority of human malignancies use telomerase to maintain telomere homeostasis. Antitelomerase therapy is therefore a promising approach for a cancer-specific therapy. The alternative lengthening of telomeres pathway (ALT) is a recombination-based, telomerase-independent mechanism of telomere length control. It is widely believed that ALT could be engaged when cancer cells escape from telomerase inhibition. However, no reports exist that would support this concept of therapy resistance. We inhibited telomerase in a human cancer cell line with a mismatch repair defect and observed a telomerase-independent, ALT-like telomere elongation. This is the first report of inducing a telomerase-independent telomere elongation in human cancer cells when telomerase is inhibited, thus describing a novel mechanism of resistance to antitelomerase therapy.

Animals↗
PubMed2004

Prostaglandin E2 is a potent regulator of interleukin-12- and interleukin-18-induced natural killer cell interferon-gamma synthesis.

Synthesis of interferon (IFN)-gamma by natural killer (NK) cells is an important pro-inflammatory event with interleukin (IL)-12 and IL-18 playing major inductive roles. However, other temporal events are likely to regulate such processes and as prostaglandin E2 (PGE2) is ubiquitous during inflammation this study tested the hypothesis that PGE2 was capable of directly modulating cytokine-induced NK cell IFN-gamma synthesis in the absence of other immune cells. Using homogeneous NK cell lines to establish direct effects, PGE2 (0.1-1 micro m) was found to suppress NK cell IFN-gamma synthesis and antagonized the potent synergistic IFN-gamma-inducing effects of IL-12 and IL-18. The actions of PGE2 were mimicked by synthetic PGE2 analogues including misoprostol and butaprost. The selective EP2 receptor agonist butaprost, but not the EP1/EP3 agonist sulprostone, suppressed IFN-gamma synthesis and exclusively competed with PGE2 for receptor binding on NK cells. Further analysis showed that PGE2 did not modulate IL-12 receptor mRNA expression and the effects of PGE2 could be mimicked by the phosphodiesterase inhibitor 3-iosobutyl-1-methylxanthine. The absence of demonstrable receptor modulation coupled with the observed suppression of IFN-gamma synthesis by both EP2 receptor-selective agonists and IBMX suggest that PGE2 acts directly on NK cells via EP2 receptors with its downstream effects on cAMP metabolism. This conclusion is further supported by findings that PGE2 and its analogues consistently elevated levels of cAMP in NK cells. The ability of PGE2 to antagonize the potent inductive signal provided by the combination of IL-12 and IL-18 supports the concept that PGE2 may play an important role in limiting innate inflammatory processes in vivo through direct suppression of NK cell IFN-gamma synthesis.

1-Methyl-3-isobutylxanthine↗
PubMed2002

An essential role for IL-13 in maintaining a non-healing response following Leishmania mexicana infection.

A comparison of the growth of Leishmania mexicana in IL-4(-/-), IL-4Ralpha(-/-) and wild-type BALB/c mice demonstrated a disease exacerbative role for IL-13 as well as IL-4. Thus, while both IL-4(-/-) and IL-4Ralpha(-/-) mice were more resistant than wild-type controls to infection with L. mexicana, IL-4Ralpha(-/-) mice, which are unresponsive to IL-13 as well as IL-4, were significantly more resistant to parasite growth than their IL-4(-/-) counterparts. Cytokine and antibody analysis revealed a Th1-biased specific response in both infected IL-4(-/-) and IL-4Ralpha(-/-) mice compared with wild-type animals. Reconstituting SCID mice with IL-4(-/-), IL-4Ralpha(-/-) or wild-type splenocytes prior to infection demonstrated that the early onset of lesion growth was dependent on the presence of lymphocytes responding to IL-4 and/or IL-13, as lesions failed to develop in only the SCID IL-4Ralpha(-/-) reconstituted mice. An independent role for IL-13 in L. mexicana infection was demonstrated by comparing disease progression in IL-13(-/-), IL-4(-/-)/IL-13(-/-) and wild-type B6/129 mice. In contrast to IL-4(-/-)/IL-13(-/-) mice, which were resistant, IL-13(-/-) mice developed lesions similar in size to wild-type animals up to week 8 post-infection. However, in contrast to wild-type mice in which disease continued to progress, lesions eventually healed in IL-13(-/-) mice, in association with the development of a Th1 response. Collectively our results suggest that IL-4 plays a critical role in early lesion development, and that IL-13 plays a crucial part in maintaining a chronic non-healing infection.

Animals↗
PubMed2002

Line-of-duty injury or illness in an Air National Guard unit.

Line-of-duty injuries or illnesses (LODs) suffered by members of Air National Guard units may demonstrate the status of unit safety, unit readiness and deployability, a potentially significant area of unit expenditures, and areas of needed health promotion. This descriptive pilot study was conducted at the unit commander's request to investigate an apparent doubling of the expected number of LODs over a recent quarterly period. Twenty cases were investigated. The vast majority of LODs were musculoskeletal in nature. Decreased fitness level (identified as increased body mass index) among males and increased age were related to increased LODs. Recommendations are given to improve tracking, identify individuals at increased risk, provide pretraining assessment, and institute health promotion focused on musculoskeletal injuries.

Adult↗
PubMedDate not supplied

Moderating factors in return to work and job stability after traumatic brain injury.

OBJECTIVE: To examine job stability moderating variables and develop a postinjury work stability prediction model. DESIGN: Multicenter analysis of individuals with traumatic brain injury (TBI) who returned for follow-up at 1, 2, and 3, or 4 years postinjury, were of working age (between 18 and 62 years of age at injury), and were working preinjury. SETTING: Six National Institute on Disability and Rehabilitation Research TBI Model System centers for coordinated acute and rehabilitation care. PARTICIPANTS: A total of 186 adults with TBI were included in the study. MAIN OUTCOME MEASURES: Job stability was categorized as stably employed (employed at all 3 follow-up intervals); unstably employed (employed at one or two of all three follow-up intervals); and unemployed (unemployed at all three follow-up intervals). RESULTS: After injury, 34% were stably employed, 27% were unstably employed, and 39% were unemployed at all three follow-up intervals. Minority group members, people who did not complete high school, and unmarried people were more likely to be unemployed. Driving independence was highly influential and significantly related to employment stability. A discriminant function analysis, which included age, length of unconsciousness and Disability Rating Scale scores at 1 year postinjury, accurately predicted job stability groupings. CONCLUSION: Data analysis provided evidence that employment stability is predictable with a combination of functional, demographic, and injury severity variables. Identification of people at risk for poor employment outcomes early on can facilitate rehabilitation planning and intervention.

Adult↗