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Biomedical subjects

P Lane

Publications and source records attributed to P Lane.

At least 19 recordsLinked to original sources
PubMed2007

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Age Factors↗
PubMed2006

Long-term clearance of patch-stage mycosis fungoides with the 308-nm laser.

In order to investigate the effectiveness of the 308-nm xenon chloride laser in the treatment of patch-stage mycosis fungoides that is refractory to topical steroids, we conducted a prospective, histologically controlled, open-label pilot study. Eight patients with stage 1A or 1B cutaneous T-cell lymphoma that was unresponsive to application of potent topical steroids received 20 treatments with the laser over 10 weeks and were then followed up for a minimum of 30 months. Three patients had a complete clinical and histological response and remained free of disease after 30 months A further three patients had complete clinical and histological clearance of disease, but experienced relapse within the 30 months follow-up period. One patient withdrew from the study and one had a partial response. Further research to establish the role of the 308-nm laser in the treatment of MF appears justified.

Adolescent↗
PubMed2005

The emergency department approach to violently injured patient care: a regional survey.

OBJECTIVE: Since the early 1990s public health workers have challenged healthcare practitioners to take an active role in violence prevention with patients aged 10-24 years. Emergency department (ED) clinicians are uniquely positioned to identify, assess, and refer youth involved in violent events. The objective of this study was to describe ED directors' estimate of the number of violently injured youth seen, the presence of established protocols or guidelines for handling youth violence, and the type of training programs offered to ED physicians regarding this issue. METHODS: The authors conducted a survey of EDs (n = 64) in the Philadelphia metropolitan region to determine the standard of ED care for violently injured youths. Half of the EDs were in urban areas and half in suburban. RESULTS: A total of 41 out of 64 (64.1%) ED directors completed and returned the written questionnaire. In addition to treating the specific injuries sustained, ED responses to youth violence primarily involved talking with patients about the events surrounding the injury. The estimated number of violently injured youth seen per month varied considerably. Twenty four directors (58.5%) estimated that their institution treated fewer than 10 per month; 10 (24.4%) reported 11-30, and seven (17.1%) mostly large urban hospitals, saw more than 30 per month. Although most hospitals reported that the staff counsels patients about safety concerns, only 17% offered their staff formal training programs on youth violence. CONCLUSIONS: To address the prevention of youth violence, EDs need specific training programs for ED staff, as well as systematic risk assessment and referral resources for structured intervention and follow up.

Adolescent↗
PubMed2004

Nodular regenerative hyperplasia of the liver and coeliac disease: potential role of IgA anticardiolipin antibody.

Nodular regenerative hyperplasia (NRH) of the liver is a rare disorder that is often associated with connective tissue disorders, haematological malignancy, or drugs, and is a cause of non-cirrhotic portal hypertension. We describe two cases of NRH in individuals with adult coeliac disease and IgA anticardiolipin antibodies. We discuss the potential impact of this observation on the understanding of the pathogenesis of NRH.

Adult↗
PubMed2003

Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis.

Both conventional and genetic engineering techniques can significantly improve the performance of animal cell cultures for the large-scale production of pharmaceutical products. In this paper, the effect of such techniques on cell yield and antibody production of two NS0 cell lines is presented. On the one hand, the effect of fed-batch cultivation using dialysis is compared to cultivation without dialysis. Maximum cell density could be increased by a factor of approximately 5-7 by dialysis fed-batch cultivation. On the other hand, suppression of apoptosis in the NS0 cell line 6A1 bcl-2 resulted in a prolonged growth phase and a higher viability and maximum cell density in fed-batch cultivation in contrast to the control cell line 6A1 (100)3. These factors resulted in more product formation (by a factor of approximately 2). Finally, the adaptive model-based OLFO controller, developed as a general tool for cell culture fed-batch processes, was able to control the fed-batch and dialysis fed-batch cultivations of both cell lines.

Adaptation, Physiological↗
PubMed2001

S-nitrosylation is emerging as a specific and fundamental posttranslational protein modification: head-to-head comparison with O-phosphorylation.

Nitric oxide (NO) is a free-radical product of mammalian cell metabolism that plays diverse and important roles in the regulation of cell function. Biological actions of NO arise as a direct consequence of chemical reactions between NO or NO-derived species and protein targets. Reactions of NO with transition metals in target proteins have garnered the most attention to date as the principal mechanism of NO signaling; nonetheless, S-nitrosylation of protein Cys residues is rapidly moving to center stage in importance. In general, however, there has been a delay in adequate appreciation of the role of S-nitrosylation in biological signaling by NO. This lag is attributed to a poor understanding of the basis for selective targeting of NO to particular thiols, and methodological limitations in accurately quantifying this modification--recent breakthroughs in concepts and methods diminish these barriers. Here, we consider the wheres and whys of protein S-nitrosylation and its basis for specificity. Protein S-nitrosylation potentially represents a ubiquitous and fundamental mechanism for posttranslational control of protein activity on a par with that of O-phosphorylation.

Animals↗
PubMed2001

Cloning, pharmacology, and tissue distribution of G-protein-coupled receptor GPR105 (KIAA0001) rodent orthologs.

It has recently been shown that UDP-glucose is a potent agonist of the orphan G-protein-coupled receptor (GPCR) KIAA0001. Here we report cloning and analysis of the rat and mouse orthologs of this receptor. In accordance with GPCR nomenclature, we have renamed the cDNA clone, KIAA0001, and its orthologs GPR105 to reflect their functionality as G-protein-coupled receptors. The rat and mouse orthologs show 80% and 83% amino acid identity, respectively, to the human GPR105 protein. We demonstrate by genomic Southern blot analysis that there are no genes in the mouse or rat genomes with higher sequence similarity. Chromosomal mapping shows that the mouse and human genes are located on syntenic regions of chromosome 3. Further analyses of the rat and mouse GPR105 proteins show that they are activated by the same agonists as the human receptor, responding to UDP-glucose and closely related molecules with similar affinities. The mouse and rat receptors are widely expressed, as is the human receptor. Thus we conclude that we have identified the rat and mouse orthologs of the human gene GPR105.

Amino Acid Sequence↗
PubMed2001

Supporting GPs whose performance gives cause for concern: the North Trent experience.

BACKGROUND: The North Trent scheme to address the problem of GPs whose performance gives cause for concern was implemented in 1997. This paper describes the structure and process of the scheme and evaluates the main outcomes. METHODS: We used non-participant observation and semi-structured interviews with representatives of the seven Health Authorities (HAs) of North Trent including medical and prescribing advisors and senior primary care managers. Twenty-one GPs who were members of the Performance Review Quartets (PRQs) were also interviewed. Qualitative data were analysed using a constant comparative method to identify emergent themes. RESULTS: Performance indicators were agreed between HAs and the profession in the seven North Trent localities. The scheme identified 18 GPs whose performance gave cause for concern, of whom 15 GPs in six practices received a formal visit. Educational plans were agreed and implemented with three GPs. The remaining 12 received administrative and clinical support. Three of the 18 GPs initially refused to co-operate with the scheme. Two of these have since agreed a practice visit following a visit by a senior local medical committee representative. The performance indicators used in the scheme have not been specific to individual GPs except those in single-handed practices. Some indicators used by PRQs related to cost effectiveness rather than quality of care for individual patients. Current resources were adequate for the small number of underperforming GPs identified by the scheme. CONCLUSIONS: The North Trent scheme has identified a number of underperforming GPs, 83% of whom have been willing to participate in a supportive intervention. The scheme will need some modification with the advent of primary care trusts and the proposed assessment and support centres.

Clinical Competence↗
PubMed2001

High-density miniaturized thermal shift assays as a general strategy for drug discovery.

More general and universally applicable drug discovery assay technologies are needed in order to keep pace with the recent advances in combinatorial chemistry and genomics-based target generation. Ligand-induced conformational stabilization of proteins is a well-understood phenomenon in which substrates, inhibitors, cofactors, and even other proteins provide enhanced stability to proteins on binding. This phenomenon is based on the energetic coupling of the ligand-binding and protein-melting reactions. In an attempt to harness these biophysical properties for drug discovery, fully automated instrumentation was designed and implemented to perform miniaturized fluorescence-based thermal shift assays in a microplate format for the high throughput screening of compound libraries. Validation of this process and instrumentation was achieved by investigating ligand binding to more than 100 protein targets. The general applicability of the thermal shift screening strategy was found to be an important advantage because it circumvents the need to design and retool new assays with each new therapeutic target. Moreover, the miniaturized thermal shift assay methodology does not require any prior knowledge of a therapeutic target's function, making it ideally suited for the quantitative high throughput drug screening and evaluation of targets derived from genomics.

Estrogen Receptor alpha↗
PubMed2001

Factors influencing the access of severely injured children and elderly patients involved in motor vehicle collisions to trauma center care.

This study was undertaken to determine factors that influence the access to trauma center care of pediatric and geriatric patients injured in motor vehicle collisions (MVC). Hospital discharge records for 1997 were obtained from the Pennsylvania Health Care Cost Containment Council and were analyzed. Of cases with an Injury Severity Score of > 15, 52.6% of elderly cases and 48.6% of pediatric cases were transported to and received their care in non-trauma center hospitals. These very high "mis-triage" rates could not be explained by differences in injury severity, body region or population density. In order to assess potential out-of-hospital factors, a file containing matched records from Emergency Medical Services (EMS) calls and hospital discharges from MVC cases across Pennsylvania for the year 1996 was constructed and analyzed. There were no significant vital signs differences between trauma center and non-trauma center cases, with the single exception of the Glasgow Coma Scale score, for both the pediatric and geriatric age groups. A reevaluation of out-of-hospital trauma triage is needed.

Accidents, Traffic↗
PubMed2000

Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts.

Rheumatoid arthritis and periodontitis are inflammatory diseases modulated by proinflammatory cytokines [e.g. interleukin (IL-1) 1 and tumour necrosis factor alpha], which activate local fibroblasts to do the following: (1) proliferate, (2) induce gene expression and (3) produce destructive metalloproteinases. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor (composed of HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear transporter) that is modulated by hypoxia. HIF-1 binds to and induces several genes containing an HIF-1 consensus-binding site, including vascular endothelial growth factor and several glycolytic enzymes. Through differential screening of a human synovial fibroblast cDNA library, we identified HIF-1alpha as a clone up-regulated by IL-1. The mRNA for HIF-1alpha subunit was increased 3-4-fold by Northern blot analysis after cells had been incubated for 3 h in the presence of IL-1. In addition, IL-1 increased the binding of the heterodimer HIF-1 to the HIF consensus sequence. These results suggest that HIF-1 might have a role in inflammation, possibly in attempting to re-establish homoeostasis.

Base Sequence↗
PubMed2000

[Actinic prurigo. An assessment of current status].

BACKGROUND AND OBJECTIVE: Actinic prurigo (AP) is a hereditary photodermatoses with typical symptoms and is quite common in North- and South-America. The key genetic factor appears to be a Native American background. In Europeans this type of AP is extremely rare; some dispute if this disease exists in Caucasians. Some newer publications postulate that these patients share HLA markers with the Native Americans. The most important differential diagnosis for AP is polymorphic light eruption which can be excluded relatively accurately by the clinical picture, typical histology and HLA pattern. PATIENTS/METHODS: The case of a female patient of Mayan ancestry living in Germany is presented. CONCLUSIONS: Since in literature sometimes cases from Europe are diagnosed as AP this is a problem of naming the disease. It would be helpful to integrate the terms hereditary or hereditaria into the name of the disease in indians.

Adult↗
PubMed2000

The autoinhibitory control element and calmodulin conspire to provide physiological modulation of endothelial and neuronal nitric oxide synthase activity.

NO production by the endothelial and neuronal isoforms of nitric oxide synthase (cNOS) is regulated on a moment-to-moment basis by calmodulin binding, triggered by transient elevations in intracellular-free calcium levels. Nonetheless, additional modes of cNOS regulation are implicit in the discoveries of stimuli that elicit a sustained increase in cNOS activity despite undetectable or transient increases in intracellular Ca2+ in endothelial cells; such stimuli include shear-stress, oestrogen, insulin or insulin-like growth factor treatment of endothelial cells. Recently, we identified a peptide insertion within the FMN-binding domain of mammalian NOSs that is unique to calcium-dependent isoforms, and not shared with inducible NOS or ancestral flavoproteins. Evidence suggests that this insertion serves as a fundamental control element, analogous to intrinsic autoinhibitory peptides that have been demonstrated to regulate activity of other calmodulin-dependent enzymes. Thus, the peptide insertion of cNOSs appears to function as structural element that is displaced upon calmodulin binding, resulting in dysinhibition of NO synthesis. Once displaced, the peptide may also be subject to transient chemical modifications and protein-protein interactions that modulate autoinhibitory function. Herein we summarize our present knowledge and speculate on mechanisms by which calmodulin and the autoinhibitory peptide conspire to regulate cNOS activity.

Animals↗
PubMed2000

A competency model for general practice: implications for selection, training, and development.

BACKGROUND: The role of the general practitioner (GP) has changed significantly over the past decade. This problem is compounded by growing concern over postgraduate attrition rates from medicine, with current estimates as high as 19%. AIM: To define a comprehensive model of the competencies required for the job role of GP. METHOD: Three independent studies were conducted to define GP competencies including (1) critical incidents focus groups with GPs, (2) behavioural coding of GP-patient consultations, and (3) critical incidents interviews with patients. Study 1 was conducted with GPs (n = 35) from the Trent region. Study 2 involved observation of GP-patient consultations (n = 33 consultations), and Study 3 was conducted with patients (n = 21), all from a Midlands-based medical practice. RESULTS: The data collected from the three studies provided strong evidence for a competency model comprising 11 categories with a summary of the associated behavioural descriptions. Example competencies included empathy and sensitivity, communication skills, clinical knowledge and expertise, conceptual thinking, and coping with pressure. CONCLUSIONS: Triangulation of results was achieved from three independent studies. The competencies derived imply that a greater account of personal attributes needs to be considered in recruitment and training, rather than focusing on academic and clinical competency alone. The model could be employed for future research in design of selection techniques for the role of GP.

Clinical Competence↗
PubMed1999

Compromised OX40 function in CD28-deficient mice is linked with failure to develop CXC chemokine receptor 5-positive CD4 cells and germinal centers.

Mice rendered deficient in CD28 signaling by the soluble competitor, cytotoxic T lymphocyte-associated molecule 4-immunoglobulin G1 fusion protein (CTLA4-Ig), fail to upregulate OX40 expression in vivo or form germinal centers after immunization. This is associated with impaired interleukin 4 production and a lack of CXC chemokine receptor (CXCR)5 on CD4 T cells, a chemokine receptor linked with migration into B follicles. Germinal center formation is restored in CTLA4-Ig transgenic mice by coinjection of an agonistic monoclonal antibody to CD28, but this is substantially inhibited if OX40 interactions are interrupted by simultaneous injection of an OX40-Ig fusion protein. These data suggest that CD28-dependent OX40 ligation of CD4 T cells at the time of priming is linked with upregulation of CXCR5 expression, and migration of T cells into B cell areas to support germinal center formation.

Abatacept↗
PubMed1999

Development and testing of the Resistiveness to Care Scale.

A conceptual model and objective scale for measuring resistiveness to care in individuals with advanced dementia of the Alzheimer type (DAT) were empirically generated from the perspective of nursing staff caregivers and through observation of residents with DAT. The resistiveness to care scale (RTC-DAT) was judged to have content validity and reduced to 13 items. Quantifiable scoring procedures and methods for rating videotapes and conducting clinical observations were developed. The RTC-DAT was tested with 68 subjects at three sites. The RTC has a range of 0-156. Initial testing provided reliability estimates of .82-.87 for internal consistency and good to excellent kappas. Criterion-related validity with observed discomfort and construct validity by factor analysis support the RTC-DAT. Measurement issues and recommendations for use in research are discussed.

Activities of Daily Living↗