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D Gorman

Publications and source records attributed to D Gorman.

At least 19 recordsLinked to original sources

FDF03, a novel inhibitory receptor of the immunoglobulin superfamily, is expressed by human dendritic and myeloid cells.

In this study, we describe human FDF03, a novel member of the Ig superfamily expressed as a monomeric 44-kDa transmembrane glycoprotein and containing a single extracellular V-set Ig-like domain. Two potential secreted isoforms were also identified. The gene encoding FDF03 mapped to chromosome 7q22. FDF03 was mostly detected in hemopoietic tissues and was expressed by monocytes, macrophages, and granulocytes, but not by lymphocytes (B, T, and NK cells), indicating an expression restricted to cells of the myelomonocytic lineage. FDF03 was also strongly expressed by monocyte-derived dendritic cells (DC) and preferentially by CD14+/CD1a- DC derived from CD34+ progenitors. Moreover, flow cytometric analysis showed FDF03 expression by CD11c+ blood and tonsil DC, but not by CD11c- DC precursors. The FDF03 cytoplasmic tail contained two immunoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences. When overexpressed in pervanadate-treated U937 cells, FDF03 was tyrosine-phosphorylated and recruited Src homology-2 (SH2) domain-containing protein tyrosine phosphatase (SHP)-2 and to a lesser extent SHP-1. Like engagement of the ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03 inhibited calcium mobilization in response to CD32/FcgammaRII aggregation in transfected U937 cells, thus demonstrating that FDF03 can function as an inhibitory receptor. However, in contrast to LAIR-1/p40, cross-linking of FDF03 did not inhibit GM-CSF-induced monocyte differentiation into DC. Thus, FDF03 is a novel ITIM-bearing receptor selectively expressed by cells of myeloid origin, including DC, that may regulate functions other than that of the broadly distributed LAIR-1/p40 molecule.

Adult↗

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Journal Article↗

Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.

Amino Acid Sequence↗

Injury prevention in Scotland--the case for a national strategy.

In children and young adults, injury overshadows other causes of death and is a major contributor to acute and long-term disability. Yet injury is more amenable to prevention than most other causes of ill health. The purpose of this paper is to present the case for the development and implementation of a national injury prevention strategy for Scotland. Systematic reviews of the evidence have identified a series of specific interventions that have been shown to reduce injury incidence, mortality or morbidity. Research suggests that over half of all traumatic deaths are avoidable in children. In addition to the responsibilities of individuals, parents, carers, schools and employers to prevent or to reduce the probability of injury, responsibility for injury prevention and the protection of the public from injury hazards lies with a range of national and local agencies in the UK. These vary across the country and are unco-ordinated. To reduce the number of deaths and disorders resulting from injury, and the costs associated with treating and caring for injured people and their families, we contend that the most pressing current need is to develop a national strategy for Scotland.

Adult↗

Occupational health practice in New Zealand.

On the basis of the national un-funded liability for work injuries and illnesses, and comparisons of health outcome and cost data to a benchmark, it can be concluded that occupational health practice in New Zealand is deficient. This deficiency persists despite recent legislative reforms and is due to a combination of Accident Rehabilitation and Compensation Insurance Corporation, health professional and industrial factors. It is clear that a comprehensive corrective strategy is needed to attend to: the up-skilling of health case managers and the medical profession in concert; and, to encouraging employers to introduce comprehensive occupational health programmes.

Benchmarking↗

The natural history of microalbuminuria in adolescents with type 1 diabetes.

OBJECTIVE: To describe the natural history of urinary albumin excretion measured initially during the first decade of type 1 diabetes in adolescents and to identify predictors of the onset and progression of microalbuminuria (MA) in this population. STUDY DESIGN: A retrospective cohort follow-up study was done on 76 adolescents whose albumin excretion rate (AER) had been determined in the first decade of their diabetes. Subjects were monitored for a mean of 6 years after initial AER testing. Those with MA were compared with a group with similar age, sex, and diabetes duration who initially had normoalbuminuria (NA). RESULTS: Of the 28 with initial MA, 9 (32%) regressed (8 to within the NA range), whereas MA was persistent in 10 (36%) and progressed in 9 (32%), 5 to overt proteinuria. Of the 47 who had initial NA, MA developed in 14 (30%) and overt proteinuria in 3 (6%). With MA status at follow-up as the dependent variable, multiple regression analysis showed that initial AER (P =.0002) and hemoglobin A1c (P =.02) measured at the same time were significant independent variables. CONCLUSIONS: These data suggest that in adolescents: (1) MA detected in the first decade of disease will persist or progress in the second decade in approximately two thirds of patients, and new MA will develop in a third of those initially normoalbuminuric; and (2) the appearance, persistence, or progression of MA is influenced in large part by metabolic control assessed by hemoglobin A1c both at initial MA screening and throughout the course of diabetes. This underlines the need for MA screening starting early in the course of type 1 diabetes in adolescents and for maintenance of good metabolic control.

Adolescent↗

Using quality function deployment to capture the voice of the customer and translate it into the voice of the provider.

BACKGROUND: Health care has a number of historical barriers to capturing the voice of the customer and to incorporating customer wants into health care services, whether the customer is a patient, an insurer, or a community. Quality function deployment (QFD) is a set of tools and practices that can help overcome these barriers to form a process for the planning and design or redesign of products and services. The goal of the project was to increase referral volume and to improve a rehabilitation hospital's capacity to provide comprehensive medical and/or legal evaluations for people with complex and catastrophic injuries or illnesses. HIGH-LEVEL VIEW OF QFD AS A PROCESS: The steps in QFD are as follows: capture of the voice of the customer, quality deployment, functions deployment, failure mode deployment, new process deployment, and task deployment. The output of each step becomes the input to a matrix tool or table of the next step of the process. CASE STUDY EXAMPLE: In 3 1/2 months a nine-person project team at Continental Rehabilitation Hospital (San Diego) used QFD tools to capture the voice of the customer, use these data as the basis for a questionnaire on important qualities of service from the customer's perspective, obtain competitive data on how the organization was perceived to be meeting the demanded qualities, identify measurable dimensions and targets of these qualities, and incorporate the functions and tasks into the delivery of service which are necessary to meet the demanded qualities. DISCUSSION: The future of providing health care services will belong to organizations that can adapt to a rapidly changing environment and to demands for new products and services that are produced and delivered in new ways.

Arizona↗

GPs' views on their role in cancer genetics services and current practice.

BACKGROUND: Increasing demand for cancer genetics services has necessitated an urgent review of how these services are organized and, in particular, identification of an effective role for primary care. OBJECTIVES: We aimed to assess the views of GPs on their role in cancer genetics services and their confidence in performing that role; to assess their understanding of cancer genetics, current practice and referral behaviour; and to identify needs for information and training to enable GPs to play an effective role in these services. METHOD: A cross-sectional questionnaire survey of GPs was conducted through general practices in SE Scotland; 397 (response rate 59.3%) GPs returned a completed questionnaire. Outcome measures were: responders' perceptions of their role in cancer genetics services; confidence within that role; understanding of cancer genetics; current practice regarding patients presenting with concerns about their family history of cancer; and perceived information and training needs. RESULTS: GPs identified their role to be: taking a family history; making appropriate referrals to specialist services; providing emotional support; teaching breast self-examination; and discussing need for screening. Lack of confidence within this role was reflected in low levels of understanding of cancer genetics and in inappropriate referral practices. Concerns were expressed about the increasingly specialist role demanded of primary care. A desire for referral guidelines and community genetics clinics was identified. CONCLUSIONS: GPs readily identify a role for themselves in cancer genetics services, but admit to a lack of confidence in this area, calling for clear referral guidelines and specialist community support. Current inappropriate referral to specialist services results from a lack of confidence in estimating cancer risk, highlighting the need for the development of clear referral criteria. Given the rapidly increasing demand for cancer genetics services and the vital role of primary care, it is important to identify a model of these services that facilitates effective involvement of GPs without further increasing their workload.

Attitude of Health Personnel↗

Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: experience in 88 patients.

OBJECT: In this study the authors sought to determine the neurological risks and potential clinical benefits of gamma knife radiosurgery for skull base meningiomas. METHODS: A consecutive series of 88 patients harboring skull base meningiomas were treated between 1990 and 1996 by using the Leksell gamma knife in a prospective clinical study that included a strict dose-volume protocol. Forty-nine patients had previously undergone surgery, and six had received external-beam radiotherapy. The median treatment volume was 10 cm3, and the median dose to the tumor margin was 16 Gy. The radiosurgical dosage to the optic nerve, the cavernous sinus, and Meckel's cave was calculated and correlated with clinical outcome. The median patient follow-up time was 35 months (range 12-83 months). Two tumors (2.3%) progressed after radiosurgery; the progression-free 5-year survival rate was 95%. At last follow-up review, 60 (68%) tumors were smaller and 26 (29.5%) remained unchanged. Clinical improvement (in vision, trigeminal pain, or other cranial nerve symptoms) occurred in 15 patients. Functioning optic nerves received a median dose of 10 Gy (range 1-16 Gy), and no treatment-induced visual loss occurred. Among nine patients with new trigeminal neuropathy, six received doses of more than 19 Gy to Meckel's cave. CONCLUSIONS: Gamma knife radiosurgery appeared to be an effective method to control the growth of most skull base meningiomas in this intermediate-term study. The risk of trigeminal neuropathy seemed to be associated with doses of more than 19 Gy, and the optic apparatus appeared to tolerate doses greater than 10 Gy. Considering the risks to cranial nerves associated with open surgery for comparable tumors, the authors believe that gamma knife radiosurgery is a useful method for the management of properly selected recurrent, residual, or newly diagnosed skull base meningiomas.

Adult↗