Papilloedema as the sole presenting feature of Chiari I malformation.
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Adult↗
Biomedical subjects
C Cooke
Publications and source records attributed to C Cooke.
A photoreceptor-specific cadherin is essential for the structural integrity of the outer segment and for photoreceptor survival.
A cadherin family member, prCAD, was identified in retina cDNA by subtractive hybridization and high throughput sequencing. prCAD is expressed only in retinal photoreceptors, and the prCAD protein is localized to the base of the outer segment of both rods and cones. In prCAD(-/-) mice, outer segments are disorganized and fragmented, and there is progressive death of photoreceptor cells. prCAD is unlikely to be involved in protein trafficking between inner and outer segments, since phototransduction proteins appear to be correctly localized and the light responses of both rods and cones are only modestly compromised in prCAD(-/-) mice. These experiments imply a highly specialized cell biological function for prCAD and suggest that localized adhesion activity is essential for outer segment integrity.
Amino Acid Sequence↗
Evaluation of the use of evidence-based angiotensin-converting enzyme inhibitor criteria for the treatment of congestive heart failure: opportunities for pharmacists to improve patient outcomes.
BACKGROUND: The under-utilization and under-dosing of angiotensin-converting enzyme inhibitors (ACEIs) in patients with congestive heart failure (CHF) continues to be a problem observed in clinical practice. OBJECTIVE: To develop and implement drug use evaluation (DUE) criteria for the use of ACEIs in patients with CHF which could be used by pharmacists to ensure that all eligible patients receive an ACEI at an appropriate dose. METHODS: A retrospective chart review of all patients discharged from the study institution with a diagnosis of CHF during the period of March 1 to July 31, 1998 was conducted using the DUE criteria developed. RESULTS: Of the 138 patients evaluated, only 68.6% were discharged on ACEI therapy. Additionally, only 40% of those discharged on an ACEI achieved target dose. Multiple regression analysis revealed that males were 2.43 times more likely to be discharged on an ACEI than females, while those on concomitant diuretics or digoxin were less likely to be discharged on an ACEI (25% and 18%, respectively). CONCLUSIONS: The application of these DUE criteria by pharmacists in hospital and community practice has the potential to improve utilization and dosing of this important class of medications for the management of the symptoms and progression of CHF.
Angiotensin-Converting Enzyme Inhibitors↗
Head injury-related road crash mortality in rural Western Australia.
BACKGROUND: The aim of the present paper was to assess the incidence of, and identify factors associated with road crash (RC)-related fatal head injuries in rural and metropolitan Western Australia. METHODS: Examination of demographics, driving behaviour and RC characteristics for RC fatalities involving a head injury (Abbreviated Injury Scale (AIS) > or = 2) between 1 January 1998 and 31 December 1999 was carried out using the State Coronial Database. RESULTS: There were 328 deaths. The median age was 28 years and 74.1% of cases were male. Seventy per cent died at the scene. Of scene survivors, 89% were transferred to a metropolitan hospital before dying. Sixty per cent of total RC and 65% of at-scene deaths occurred in rural areas. Single-vehicle crashes comprised 45% of total crashes, of which 72.8% occurred in rural locations. Poor driver behaviour was identified in 53% of deaths. Ethanol was implicated in 29.8% of deaths, other intoxicating drugs were implicated in 19.2%, speeding was implicated in 19.5%, and lack of safety restraints/devices was implicated in 22%. Poor driver behaviour was identified in 72% of single-vehicle deaths, compared with 38% of multivehicle crashes (P < 0.001). Rural people comprised 61% of rural crash victims. Ninety-one per cent of rural victims died in rural crashes. The incidence of RC death associated with head injury in the rural population is 13.4 deaths/100 000 per year, more than double that for the metropolitan population (6.4 deaths/100 000 per year; P < 0.001). CONCLUSION: The rural population of Western Australia is overrepresented in head injury-related RC deaths. Single-vehicle crashes where unsafe driving behaviour is implicated comprise a large proportion of these. Strategies to reduce unsafe driving practices aimed at rural drivers are necessary.
Accidents, Traffic↗
The association between racism and high blood pressure among African Americans.
National attention is currently being directed toward assessing the association between racism as a stressor and high blood pressure (HBP) among African Americans. Within this context, however, very little research is designed to elucidate the viewpoints of African Americans with HBP on this topic area. The purpose of this article is to explore, critique, and elaborate upon the study of racism as it relates to HBP research. The first portion of this paper reviews the existing literature in this field. Limitations of the current research are outlined. Insights gained as 30 African Americans with HBP talked about racism as a stressor and how it affected their health are subsequently highlighted. Lastly, suggestions for future studies on racism and HBP are postulated.
Black or African American↗
Glutamic acid mutagenesis of retinoblastoma protein phosphorylation sites has diverse effects on function.
The retinoblastoma tumor suppressor gene (Rb) has many functions within the cell including regulation of transcription, differentiation, apoptosis, and the cell cycle. Regulation of these functions is mediated by phosphorylation at as many as 16 cyclin-dependent kinase (CDK) phosphorylation sites in vivo. The contribution of these sites to the regulation of the various Rb functions is not well understood. To characterize the effect of phosphorylation at these sites, we systematically mutagenized the serines or threonines to glutamic acid. Thirty-five mutants with different combinations of modified phosphorylation sites were assayed for their ability to arrest the cell cycle and for their potential to induce differentiation. Only the most highly substituted mutants failed to arrest cell cycle progression. However, mutants with as few as four modified phosphorylation sites were unable to promote differentiation. Other mutants had increased activity in this assay. We conclude that modification of Rb phosphorylation sites can increase or decrease protein activity, that different Rb functions can be regulated independently by distinct combinations of sites, and that the effects of modification at any one site are context dependent.
Bone Neoplasms↗
Utilization of splicing elements and polyadenylation signal elements in the coupling of polyadenylation and last-intron removal.
Polyadenylation (PA) is the process by which the 3' ends of most mammalian mRNAs are formed. In nature, PA is highly coordinated, or coupled, with splicing. In mammalian systems, the most compelling mechanistic model for coupling arises from data supporting exon definition (2, 34, 37). We have examined the roles of individual functional components of splicing and PA signals in the coupling process by using an in vitro splicing and PA reaction with a synthetic pre-mRNA substrate containing an adenovirus splicing cassette and the simian virus 40 late PA signal. The effects of individually mutating splicing elements and PA elements in this substrate were determined. We found that mutation of the polypyrimidine tract and the 3' splice site significantly reduced PA efficiency and that mutation of the AAUAAA and the downstream elements of the PA signal decreased splicing efficiency, suggesting that these elements are the most significant for the coupling of splicing and PA. Although mutation of the upstream elements (USEs) of the PA signal dramatically decreased PA, splicing was only modestly affected, suggesting that USEs modestly affect coupling. Mutation of the 5' splice site in the presence of a viable polypyrimidine tract and the 3' splice site had no effect on PA, suggesting no effect of this element on coupling. However, our data also suggest that a site for U1 snRNP binding (e.g., a 5' splice site) within the last exon can negatively effect both PA and splicing; hence, a 5' splice site-like sequence in this position appears to be a modulator of coupling. In addition, we show that the RNA-protein complex formed to define an exon may inhibit processing if the definition of an adjacent exon fails. This finding indicates a mechanism for monitoring the appropriate definition of exons and for allowing only pre-mRNAs with successfully defined exons to be processed.
HeLa Cells↗
Adding other antipsychotics to clozapine.
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Acute Disease↗
Amrinone and amiodarone: serious confusion in the intravenous line.
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Amiodarone↗
The snRNP-free U1A (SF-A) complex(es): identification of the largest subunit as PSF, the polypyrimidine-tract binding protein-associated splicing factor.
We have previously shown that a specific monoclonal antibody prepared against the U1A protein, MAb 12E12, is unique in its ability to recognize a form of U1A which is not associated with the U1snRNP. This unique form of U1A, termed snRNP-free U1A or SF-A, was found to be complexed with a novel set of non-snRNP proteins (O'Connor et al., 1997, RNA 3:1444-1455). Here we demonstrate that the largest protein in these SF-A complex(es), p105, is the polypyrimidine-tract binding protein-associated factor (PSF), an auxiliary splicing factor. We show that PSF copurifies and co-immunoprecipitates with SF-A from 293T cell nucleoplasm and that it interacts with SF-A in vitro. In addition, we show that MAb 12E12 inhibits both splicing and polyadenylation in an in vitro coupled splicing and polyadenylation reaction. This suggests that SF-A and/or the SF-A complex(es) perform an important function in both processing reactions and possibly in last exon definition.
Amino Acid Sequence↗
Role of Ca2+/calmodulin-dependent phosphatase 2B in thrombin-induced endothelial cell contractile responses.
Thrombin-induced Ca2+ mobilization, activation of Ca2+/calmodulin-dependent myosin light chain (MLC) kinase (MLCK), and increased phosphorylation of MLCs precede and are critical to endothelial cell (EC) barrier dysfunction. Net MLC dephosphorylation after thrombin is nearly complete by 60 min and involves type 1 phosphatase (PPase 1) activity. We now report that thrombin does not alter total PPase 1 activity in EC homogenates but rather decreases myosin-associated PPase 1 activity. The PPase 1 inhibitor calyculin fails to prevent thrombin-induced MLC dephosphorylation. However, thrombin significantly increased the activity of Ca2+-dependent PPase 2B in EC homogenates (approximately 1.5- to 2-fold), with PPase 2B activation correlating with phosphorylation of the PPase 2B catalytic subunit. Western immunoblotting revealed PPase 2B to be present in cytoskeletal EC fractions, with specific PPase 2B inhibitors such as cyclosporin (200 nM) and deltamethrin (100 nM to 1 microM) attenuating thrombin-induced cytoskeletal protein dephosphorylation, including EC MLC dephosphorylation. These results suggest a model whereby thrombin-inducible contraction is determined by the phosphorylation status of EC MLC regulated by the balance between EC MLCK, PPase 1 (constitutive), and PPase 2B (inducible) activities.
Animals↗
Reflections on the health care team: my experiences in an interdisciplinary program.
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Education, Medical↗
Bronchial blood vessel dimensions in asthma.
The extent to which the bronchial vasculature contributes to airway wall thickening in large and small airways in patients with asthma is unknown. The aim of this study was to quantify the number and the area occupied by blood vessels in the airway submucosa of patients with and without asthma. We used the monoclonal antibody Factor VIII to measure the blood vessels between the airway basement membrane and the outer border of the smooth muscle. In large cartilaginous airways in patients with fatal asthma, the number and area of large blood vessels were increased and the number and area of small blood vessels were decreased, compared with that in patients with nonfatal asthma and control subjects. However, the total number of blood vessels and the total area occupied by blood vessels per square millimeter in the airway submucosa were similar in patients with fatal asthma or nonfatal asthma and in control subjects in all airway size groups. Blood vessels were distended to a mean value of 80% of their estimated maximal area. The increased number of larger vessels in patients with fatal asthma raises the possibility that vascular congestion associated with an acute severe asthma attack may distend blood vessels. The finding of similar numbers of blood vessels per square millimeter of submucosa in control subjects and in patients with asthma suggests that blood vessels increase in number in patients with asthma only in proportion to increased airway wall area. It is unlikely that submucosal vessels could act as capacitance vessels and significantly alter inner airway wall thickness.
Adult↗
Arthrodesis of the first metatarsophalangeal joint to salvage failed silicone implant arthroplasty.
Between 1987 and 1992, all patients presenting to the senior author with a symptomatic failed silicone implant arthroplasty refractory to conservative treatment were converted to a metatarsophalangeal joint arthrodesis. Internal fixation was achieved with either dual intrameduilary threaded Steinmann pins or an obliquely placed AO compression screw and a three- or four-hole one-third tubular dorsal neutralization plate. Bone grafting was used to maintain hallux length. Successful arthrodesis was achieved in all five feet in patients with rheumatoid arthritis. Subjectively, patients improved from an average of 0.69 before arthrodesis to 4.89 after arthrodesis. The average walking tolerance improved from 1.11 to 4.80, and the overall level of satisfaction improved from 0.0 to 4.79. The patient's ability to wear shoes improved from 0.87 to 3.1. Successful arthrodesis produces a foot that is more functional and durable than excisional arthroplasty. Subjectively, these patients stated that their level of pain, walking tolerance, and overall satisfaction improved significantly after the arthrodesis. Clinically, there was no evidence of transfer lesions, tenderness, or hallux subluxation. Hallux length was well maintained after surgery with bone grafting, but it was more difficult to obtain the alignment goals. The average postoperative metatarsophalangeal dorsiflexion angle was 15.6 degrees and the first metatarsophalangeal angle was 3.1 degrees. Despite this, patient satisfaction was high. Arthrodesis of the first metatarsophalangeal joint using a bone graft to salvage failed silicone implant arthroplasty produces acceptable subjective and radiographic results. Although technically demanding, it provides long-term stability to the hallux, restores weightbearing, and allows for maintenance of a propulsive gait. We recommend this procedure instead of an excisional arthroplasty to maintain high level of function and overall patient satisfaction.
Adult↗
The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics.
Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma. In cases of fatal asthma (n = 10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n = 10), and control cases (sudden death with no history of respiratory illness, n = 10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin. Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p < 0.001). Eosinophils were increased (p < 0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r = 0.60; p < 0.0001), and to a lesser extent in the nonfatal (r = 0.34; p = 0.001) and control groups (r = 0.32; p = 0.001). These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.
Adolescent↗
Induction of apoptosis by pyrrolidinedithiocarbamate and N-acetylcysteine in vascular smooth muscle cells.
Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAC) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, and vascular endothelial cells. We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells. In rat aortic smooth muscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpression of Bcl-2 suppressed vascular smooth muscle cell death caused by PDTC and NAC. The viability of rat aortic smooth muscle cells decreased within 3 h of treatment with PDTC and was reduced to 30% at 12 h. The effect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viability in rat and human aortic smooth muscle cells. In contrast, neither PDTC nor NAC reduced viability in human aortic endothelial cells. The use of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.
Acetylcysteine↗
Variability of airway structure and inflammation in normal subjects and in cases of nonfatal and fatal asthma.
The quantitative assessment of airway inflammation in patients with apparently similar clinical severity of asthma has yielded variable results. The aim of this study was to assess the variability of inflammatory cell counts and airway structure in large and small airways from subjects with and without asthma, and to calculate the number of cases required to detect significant differences between disease groups. Three serial transverse sections, 20 microns apart, were examined from cartilaginous and membranous bronchioles. Airway dimensions measured were the areas and perimeters defined by the luminal surface of the airway epithelium, basement membrane, outer border of airway smooth muscle, and surrounding border of the airway adventitia. Airway wall components measured were the areas of airway smooth muscle, mucous glands and cartilage. The numbers (per mm of basement membrane) of lymphocytes, eosinophils, neutrophils and plasma cells were counted using haematoxylin and eosin staining and mast cells were counted in sections stained with Toluidine blue. Measurements were repeated by two or three observers. The coefficient of variation (CV) was used to assess intraairway, intraobserver and interobserver variability. For airway dimensions the mean (+/- SD) CV within airways was 3.8% +/- 2.1%, within observers was 3.7% +/- 1.8% and between observers, 3.4% +/- 1.8%. For airway wall components, the CV within airways was 10.7% +/- 4.6%, and between observers was 8.8% +/- 2.2%. For cell counts, the CV within airways was 20.8% +/- 12.5%, within observers was 8.3% +/- 3.7% and between observers, 9.6% +/- 4.6%. There were no significant differences in variability between cases with and without asthma. Intra-airway variability was higher (p < 0.05) in membranous airways (5.6% +/- 1.7%) than in large cartilaginous airways (2.3% +/- 1.1%). We estimate that between 5 and 15 cases in each group would be required to detect differences of 50-100% between groups, depending on the parameter being compared. These findings suggest that airway structure and inflammatory cell numbers are uniform throughout the bronchial tree in normal and asthmatic cases, and that small samples of large or small airways are likely to be representative when comparing cases.
Adult↗
The pathology of hanging deaths in Western Australia.
We present here the results of a prospective study of the pathology of 233 fatalities due to hanging in Western Australia (WA). The deaths occurred during the 5 year period 1988-92. Post mortem examination of these cases was undertaken according to a standardised protocol by forensic pathologists of this office. Post mortem findings of a further 37 cases examined by medical practitioners in rural WA are also reviewed, making a useful comparison. Petechial hemorrhages, as a hallmark of asphyxiation, were present in 113 of the 233 cases (48%). An observable ligature mark to the skin of the neck was seen in 230 cases (99%). Injury to the tissues of the neck was identified in 122 cases (52%), more commonly with complete suspension of the body (62%) than incomplete suspension (46%). Neck injury was essentially equally prevalent with a slip-knot (58%) or a fixed knot (60%). Other fresh injuries besides the neck injury were present on the deceased's body in 80 cases (34%). In the 37 non-metropolitan cases, an observable ligature mark to the skin of the neck was recorded in 30 (81%). Petechial hemorrhages were described in 3 cases (8%). Internal neck injury was apparently observed in 10 cases (27%), although precise detail adequately identifying the site of injury was given in only 2 cases (5%).
Adolescent↗