Varied ecosystems need different fire protection.
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Ecosystem↗
Biomedical subjects
M Dickinson
Publications and source records attributed to M Dickinson.
Solving the mystery of insect flight.
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Animals↗
Cellular stress inhibits vascular smooth muscle relaxation.
PURPOSE: Cellular stress has been shown to induce a group of proteins called heat shock proteins (HSPs). Recent evidence suggests that a group of small HSPs may modulate vascular smooth muscle contraction (HSP27) and/or relaxation (HSP20). In this investigation, we hypothesized that cellular stress would alter contraction and/or relaxation of intact vascular smooth muscles and would lead to changes in the induction and/or phosphorylation of the small HSPs. METHODS: Bovine carotid arteries were obtained from an abattoir, and physiologic contractile responses were determined in a muscle bath. Phosphorylation state-specific antibodies were produced and characterized against HSP27. Phosphorylation events were determined with phosphorylation state-specific antibodies or whole-cell phosphorylation and two-dimensional gel electrophoresis. RESULTS: Cellular stress induced by arsenite or heat shock did not alter basal tone or the magnitude of contractions induced by serotonin or high extracellular potassium chloride. However, cellular stress led to inhibition of forskolin and sodium nitroprusside-induced vasorelaxation. This impaired vasorelaxation was associated with increases in the phosphorylation of HSP27 and decreases in forskolin-induced phosphorylation of HSP20. CONCLUSION: Cellular stress, which leads to increases in the phosphorylation of HSP27, inhibits cyclic nucleotide-dependent vascular relaxation and cyclic nucleotide-dependent increases in the phosphorylation of HSP20.
Animals↗
The macromolecular associations of heat shock protein-27 in vascular smooth muscle.
BACKGROUND: Behavioral stress is a risk factor for hypertension and atherosclerosis. Stress leads to increases in the expression and phosphorylation of heat shock proteins (HSPs) in vascular smooth muscle. Two small heat shock proteins, HSP27 and HSP20, have been implicated in the regulation of the contraction and relaxation of smooth muscle. We hypothesized that stress-induced alterations in the phosphorylation of HSP27 would effect the macromolecular associations of the small HSPs. METHODS: Bovine carotid artery smooth muscle was treated with buffer alone or with the chemical stressor, arsenite. HSP27 phosphorylation was determined with isoelectric focusing immunoblotting. Macromolecular interactions were determined with subcellular fractionation, molecular sieving, and glutaraldehyde cross-linking and immunoblotting. RESULTS: Arsenite treatment led to increases in the phosphorylation of HSP27, a redistribution of some HSP27 from a cytosolic to a particulate fraction and to the formation of larger macromolecular aggregates of HSP27. Glutaraldehyde cross-linking and immunoblotting demonstrated that HSP27 existed in monomeric and dimeric forms, which suggested that the large aggregates were not simply aggregates of HSP27 but contained other proteins. CONCLUSIONS: Cellular stress leads to increases in the phosphorylation of HSP27 and to changes in the macromolecular associations of HSP27 in intact vascular smooth muscles. The functions of the small HSPs in the vascular smooth muscle may be dependent on both phosphorylation and macromolecular associations.
Animals↗
Stress causes decrease in vascular relaxation linked with altered phosphorylation of heat shock proteins.
Cyclic nucleotide-dependent vascular relaxation is associated with increases in the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in phosphorylation of another small HSP, HSP27, is associated with impaired cyclic nucleotide-dependent vascular relaxation. Expression of HSPs is altered by exposure to several types of cellular stress in vitro. To determine if behavioral stress in vivo alters vascular expression and phosphorylation of the small HSPs and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or remained in their home cage. Stress impaired relaxation of aorta to forskolin, which activates adenylyl cyclase, and sodium nitroprusside, which activates guanylyl cyclase. This was associated with an increase in the aortic expression and phosphorylation of HSP27, which was localized to the vascular smooth muscle, but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27 inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20. The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced cyclic nucleotide-dependent vascular smooth muscle relaxation in response to behavioral stress in vivo, an effect similar to that observed previously in response to cellular stress in vitro.
Animals↗
Phosphorylation of the small heat shock-related protein, HSP20, in vascular smooth muscles is associated with changes in the macromolecular associations of HSP20.
Cyclic nucleotide-dependent vasorelaxation is associated with increases in the phosphorylation of a small heat shock-related protein, HSP20. We hypothesized that phosphorylation of HSP20 in vascular smooth muscles is associated with alterations in the macromolecular associations of HSP20. Treatment of bovine carotid artery smooth muscles with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and the adenylate cyclase activator, forskolin, led to increases in the phosphorylation of HSP20 and dissociation of macromolecular aggregates of HSP20. However, 3-isobutyl-1-methylxanthine and forskolin treatment of a muscle that is uniquely refractory to cyclic nucleotide-dependent vasorelaxation, human umbilical artery smooth muscle, did not result in increases in the phosphorylation of HSP20 or to dissociation of macromolecular aggregates. HSP20 can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase (PKA) in both carotid and umbilical arteries and this phosphorylation of HSP20 is associated with dissociation of macromolecular aggregates of HSP20. Activation of cyclic nucleotide-dependent signaling pathways does not lead to changes in the macromolecular associations of another small heat shock protein, HSP27. Interestingly, the myosin light chains (MLC20) are in similar fractions as the HSP20, and phosphorylation of HSP20 is associated with changes in the macromolecular associations of MLC20. These data suggest that increases in the phosphorylation of HSP20 are associated with changes in the macromolecular associations of HSP20. HSP20 may regulate vasorelaxation through a direct interaction with specific contractile regulatory proteins.
1-Methyl-3-isobutylxanthine↗
The roles of acetaldehyde dehydrogenases in Saccharomyces cerevisiae.
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Aldehyde Oxidoreductases↗
The quality of general dental care: public and users' perceptions.
BACKGROUND: Systematic evidence about how the public and users perceive and experience the quality of general dental care is in short supply, particularly in light of the recent changes in the general dental service. The study reported here attempted to fill this gap. OBJECTIVES: To identify the criteria the public and users adopt in evaluating the quality of general dental care, and to identify the extent and nature of perceived concerns with general dental care. DESIGN: Postal questionnaires were sent to random samples of adults living in an inner city area (I) and semi-rural area (R) in southern England. Fifty six per cent (1499) in area R and 48% (1388) in area I completed the questionnaire after four mailings. Follow up face-to-face interviews were done with a purposive subsample (n = 50) of responders from the postal survey. MAIN MEASURES: Public/user views about quality of dental care were measured through groups of questions about the importance of and satisfaction with different aspects of dental care (access/availability including cost; facilities; technical skills; and interpersonal care) and a scale (Dentsat) measuring general satisfaction was constructed from questions on different aspects of care. RESULTS: Evaluation of quality of general dental care from the users' point of view hinges on perceived technical skills, particularly pain management. Major dissatisfaction stems from concerns about costs of dental care and privatisation. CONCLUSIONS: The criteria adopted by the public/users to assess general dental care are similar to other areas of health care, apart from the priority placed on technical skills and pain management. However, the major source of decline in satisfaction with the quality of general dental care is the barrier to access created by the rising cost of dental care and the increasing involvement of dentists in private practice. This evidence suggests that the public and users find the drift towards private practice and away from NHS practice a major source of concern.
Consumer Behavior↗
Radical cystectomy for elderly patients with bladder carcinoma: an updated experience with 404 patients.
BACKGROUND: The authors evaluated the experiences at their institution with radical cystectomy and urinary diversion performed on elderly bladder carcinoma patients to determine whether age had an impact on the clinical or functional results for this group of patients. METHODS: Between August 1971 and December 1996, 404 patients age 70 years or older (median age, 74 years) underwent radical cystectomy and urinary diversion for invasive bladder carcinoma: 352 (87%) were ages 70-79 years and 52 (13%) were age 80 years or older. Data analyzed included the following: perioperative mortality; early (within 90 days after surgery) and late (more than 90 days after surgery) postoperative complications, related and unrelated to the urinary diversion; length of hospital stay; pathologic staging; and clinical outcome. These data were then compared with those for 762 patients younger than 70 years (median age, 61 years) who underwent the same procedure during the same time period. RESULTS: The overall mortality rate for patients age 70 years or older was 2.8% (3.2% for those ages 70-79 years, 0% for those age 80 years or older), compared with 2% for patients younger than 70 years. The early complication rate for patients age 70 years or older was 32%, compared with 25% for patients younger than 70 years. Patients age 80 years or older had a similar early complication rate of 29%. Late postoperative complications occurred in 12.4% of patients age 70 years or older, compared with 22.8% of patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 3-year and 5-year overall survival rates for patients age 70 years or older were 60% and 53%, respectively, compared with 68% and 63%, respectively, for patients younger than 70 years (P=0.001). There was no statistical difference between the groups when rates of disease recurrence were compared (P=0.3627). The 5-year recurrence rate for patients age 70 years or older was 35%, compared with a 5-year recurrence rate of 31% for patients younger than 70 years. CONCLUSIONS: These data suggest that an aggressive, curative, radical surgical approach and urinary diversion may be a viable treatment strategy for properly selected elderly patients who are in generally good health and require definitive therapy for invasive bladder carcinoma.
Aged↗
Thrombin activates MAPKAP2 kinase in vascular smooth muscle.
PURPOSE: Thrombin mediates hemostasis by promoting thrombus development and vasospasm, which reduces the size of the arterial injury. Thrombin stimulation of vascular smooth muscle is associated with activation of mitogen-associated protein kinase. The purpose of this investigation was to determine the subsequent cellular signaling events in thrombin-stimulated vascular smooth muscle contraction. METHODS: Contractile responses of bovine carotid artery smooth muscle were determined in a muscle bath and compared with phosphorylation events with two-dimensional gel electrophoresis. The activity of a novel kinase, mitogen-activated protein kinase-activated protein-2 kinase (MAPKAP2 kinase), was determined by immunoprecipitation and a phosphotransferase assay. A small heat shock protein, HSP27, was identified with immunoblotting. RESULTS: Thrombin induces contraction of vascular smooth muscle and is associated with increased activity of MAPKAP2 kinase and increased phosphorylation of HSP27. Multiple isoforms of HSP27 are the predominant phosphoproteins in vascular smooth muscle, and peptide mapping suggests that the isoforms of HSP27 are structurally related and phosphorylated within similar peptide sequences. CONCLUSIONS: Activation of the MAPKAP2 kinase pathway and phosphorylation of HSP27 are associated with thrombin-induced contraction of vascular smooth muscle.
Animals↗
Cutaneous zygomycosis (mucormycosis) complicating endotracheal intubation: diagnosis and successful treatment.
Diagnosis and successful therapy for primary cutaneous zygomycosis (mucormycosis) that complicated the securing of an endotracheal tube with cloth tape. Primary cutaneous mucormycosis is a rare fungal infection noted most often in immunosuppressed individuals. Cloth tape, of the type commonly used to secure endotracheal tubes, often is contaminated with fungal spores. In the case reported here, cloth tape securing the endotracheal tube was the probable vector for transmission of zygomycosis to a moderately imunocompromised host. Rapid diagnosis and combined medical and surgical therapy resulted in a favorable outcome.
Adult↗
Heat shock protein expression in umbilical artery smooth muscle.
Postpartum vasospasm in the umbilical arteries may be due to impaired vasorelaxation secondary to alterations in the expression of heat shock proteins. The contractile responses of pre- and full-term bovine umbilical artery smooth muscles were determined in a muscle bath. Heat shock protein expression was determined in bovine and human arterial tissues using western blotting with specific antisera. Full-term bovine and human umbilical artery smooth muscle was refractory to relaxation induced by the nitric oxide donor, sodium nitroprusside. This impaired vasorelaxation was associated with the expression of the inducible form of the heat shock protein, HSP70i, and increases in the expression of the small heat shock protein, HSP27. Small heat shock proteins have been implicated in modulating contraction and relaxation responses in vascular smooth muscles. Thus, alterations in heat shock protein expression may play a role in umbilical artery vasospasm.
Analysis of Variance↗
Renal angiomyolipoma: optimal treatment based on size and symptoms.
The natural history of renal angiomyolipoma is not well delineated. Current management options include observation, embolization, and partial or total nephrectomy. Recommendations for treatment are usually based on the patient's symptoms or the size of the lesion. In an effort to help define the optimal treatment of renal angiomyolipomas, we reviewed our experience over the last 10 years with these tumors. We performed a retrospective study of 37 patients (48 renal units) diagnosed with renal angiomyolipoma over a ten year period at our medical center (mean follow-up 40 months, range 1 month-12 years). Lesions were classified as small (< 4 cm), medium (4-8 cm) or large (> 8 cm) based on the single largest lesion in each kidney. The relationship between the size, symptoms and treatment was reviewed. Patients were also analyzed with regard to the diagnosis of tuberous sclerosis. Our findings indicate renal angiomyolipomas less than 4 cm (21/37 patients) tend to be asymptomatic and generally do not require intervention. Angiomyolipomas greater than 8 cm were responsible for significant morbidity and generally require treatment (5/6). Patients with tuberous sclerosis made up one half (3/6) of the large lesions. Medium-sized lesions had a less predictable natural history, with 54% (7/13) requiring intervention to treat hemorrhagic complications. Small asymptomatic lesions (< 4 cm) tend to remain stable but should be periodically evaluated. Medium-sized lesions (4-8 cm) have the most variable behavior. These lesions should be followed closely with serial imaging studies, and if significant changes in size or symptoms are noted, or the patient is at risk for flank trauma, elective intervention should be initiated promptly to increase the chances of renal salvage. Large asymptomatic angiomyolipomas (> 8 cm) will most likely become symptomatic and should be treated electively prior to the development of symptoms and potential complications.
Adolescent↗
Airway management training using the laryngeal mask airway: a comparison of two different training programmes.
Nurses without prior experience in the use of the laryngeal mask airway (LMA) were randomly allocated to one of two groups to be trained in the emergency technique of insertion of an LMA. Group A (32 nurses) were trained only on a manikin and group B (20 nurses) were trained on a manikin and with live anaesthetised patient practice in theatre (five successful insertions). Without further practice, both groups were asked to insert an LMA in a live patient in theatre 3 months after initial training. Three attempts per nurse were allowed. In group A, 75% passed the LMA successfully at the first attempt, 22% at the second attempt and 3% (one nurse) at the third attempt. In group B, 80% were successful at first attempt and 20% at the second attempt. Skill performance and retention were shown to be high following either training method, with no significant difference between the performance of either group (chi 2). We have shown that manikin-only training in the emergency technique for LMA insertion is as effective as live patient training. It is proposed that manikin training alone may be adopted as a future training modality if, as is expected, the use of the LMA in resuscitation becomes more commonplace.
Cardiopulmonary Resuscitation↗
Small heat shock proteins and vasospasm in human umbilical artery smooth muscle.
Human umbilical artery smooth muscle is uniquely refractory to cyclic nucleotide-dependent vasorelaxation. Small heat shock proteins (HSPs) have been implicated as contractile regulatory proteins. Thus, we hypothesized that alterations in the phosphorylation of small HSPs may contribute to human umbilical artery smooth muscle vasospasm. Physiologic contractile responses were determined in a muscle bath and compared with phosphorylation events determined with whole-cell phosphorylation and 2-dimensional gel electrophoresis. Precontraction of bovine carotid artery smooth muscle with serotonin followed by relaxation with forskolin was associated with increases in the phosphorylation of HSP27 and HSP20. Precontraction of umbilical artery with serotonin followed by forskolin treatment led to increases in the phosphorylation of HSP27. However, the umbilical artery smooth muscle did not relax, nor was there an increase in the phosphorylation of HSP20 with forskolin treatment. These data suggest that impaired cyclic nucleotide-dependent relaxation of umbilical artery smooth muscle is associated with a lack of phosphorylation of HSP20.
Colforsin↗
Relationship of tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer.
The purpose of this investigation was to evaluate the relationship between tumor angiogenesis and nuclear p53 accumulation in invasive bladder cancer. We studied 161 patients with invasive transitional cell carcinoma of the bladder who had previously undergone radical cystectomy. Analysis was performed to determine the presence of p53 nuclear accumulation and extent of tumor-associated angiogenesis. p53 status identified a group of patients at high risk for tumor progression (p53-altered tumors), and microvessel density determinations added additional prognostic information by identifying a subset of aggressive tumors within the wild-type p53 subgroup. At 5 years, patients with tumors exhibiting no evidence of p53 alterations and low microvessel counts demonstrated 3% recurrence and 88% survival, compared to 43% recurrence and 59% overall survival for patients with intermediate vessel counts and 61% recurrence and 43% overall survival for patients with the highest vessel counts (P < 0.001 and P = 0.003, respectively). Angiogenesis also provides additional prognostic information to patients with tumors that demonstrate p53 alterations. An association between angiogenesis and p53 status did exist (P = 0. 05); however, 27% of the tumors that showed no evidence of p53 alterations exhibited high microvessel counts, and 26% of tumors with evidence of p53 alterations had low microvessel counts. Tumor-associated angiogenesis adds additional useful prognostic information to that which is obtained from p53 status in patients with invasive transitional cell carcinoma of the bladder. Although an association between p53 status and the degree of angiogenesis was identified, other factors appear to play a role in the regulation of tumor-induced neovasularization.
Biomarkers, Tumor↗
Type I A-kinase is activated by platelet-derived growth factor in mesangial cells.
In the glomerular mesangial cell, platelet-derived growth factor (PDGF) activates several signal transduction pathways. We examined the effect of PDGF on cAMP production and on cAMP-dependent protein kinase (A-kinase) activation. In mesangial cells, PDGF stimulated cAMP production in a dose- and time-dependent manner. This effect of PDGF was not prevented by pre-incubation with 50 microM indomethicin. PDGF also activated type I A-kinase, the predominate A-kinase isoform in mesangial cells, measured either by a decrease in A-kinase photoaffinity labeling with 8-azido-[32P]-cAMP, or by an increase in A-kinase substrate phosphorylation. The activation of A-kinase by PDGF is not dependent on the intermediate production of prostaglandins or cGMP. These data suggest that A-kinase participates in PDGF-induced signaling events in mesangial cells.
1-Methyl-3-isobutylxanthine↗
Cell death in the CNS of the Wnt-1 mutant mouse.
Using the benzothiazolium-4-quinolium dye, TO-PRO-1, to detect cell death in live embryos, we labeled a developmental series of Wnt-1 null mutant and wild type embryos to determine if cell death contributed to the absence of the midbrain and rostral metencephalon observed in Wnt-1 mutant embryos. We found that there is no detectable cell death at early somite stages in Wnt-1 mutant embryos. However, we detected a significant, but transient, population of dying cells within the anterior dorsal metencephalon in 20-29 somite stage embryos. These cells located in the anterior dorsal metencephalon also stain positive using the TUNEL technique that utilizes terminal transferase to label DNA fragments that are typical in the nuclei of apoptotic cells. Thus, programmed cell death plays a role in the loss of the metencephalon, but apparently does not contribute to the earliest aspect of the mutant phenotype, namely the loss of the midbrain.
Animals↗