Automated external defibrillators.
Explore the source record for details and available documents.
Aircraft↗
Biomedical subjects
A Jaffe
Publications and source records attributed to A Jaffe.
Difficult asthma: defining the problems.
A retrospective survey was undertaken of children with difficult asthma, attending a respiratory clinic. The clinical and laboratory profiles of asthmatic children who were poorly controlled on > or = 800 microg of inhaled corticosteroids (ICS) were studied and compared to children well-controlled on > or = 800 microg ICS. Assessments were made of atopy, growth, lung function, treatment adherence, home environment, and responsiveness to corticosteroids (CS). Fiftyseven "difficult" and 23 well-controlled children were studied. Significant differences in the home environment were identified. Smoking was significantly more common in the difficult-to-control group. Nine children had alternative diagnoses. Poor CS responsiveness was present in 10 children. Adverse home environments, poor treatment supervision, alternative diagnoses, and unresponsiveness to CS were the most important factors in difficult asthma. A full assessment, including bronchoscopy, is indicated to avoid unnecessary increases in CS to doses that could cause side-effects.
Administration, Inhalation↗
A novel form of platelet-type 12-lipoxygenase mRNA in human vascular smooth muscle cells.
The lipoxygenase pathway has been implicated in the growth, migration, and contraction of vascular smooth muscle cells (VSMCs). However, the precise type of lipoxygenase present in the vascular wall has not been characterized. In this study, we used a specific reverse-transcriptase polymerase chain reaction method with 2 sets of specific primers on total RNA and polyA (+)RNA of normal human VSMCs prepared from umbilical artery. Two forms of platelet-type 12-lipoxygenase mRNA were present in human VSMCs: the already published form cloned from human erythroleukemia cells and a variant form of platelet-type 12-lipoxygenase, which includes 2 additional sequences consistent with the 2 introns (D and E). This novel form of 12-lipoxygenase poly A (+)RNA was downregulated by lipopolysaccharide (10 ug/ml) and upregulated by epidermal growth factor (100 ng/ml) but was not affected by angiotensin II (10(-7) mol/l). We developed a rabbit anti-human platelet-type 12-lipoxygenase polyclonal antibody directed against a 24-amino acid peptide encoded within exon 4. Western immunoblotting of protein extracted from VSMCs and umbilical artery and platelet extract with this antibody showed a coordinate 110-kDa protein and the already-described 70-kDa band detected in platelets and cord homogenate. Another 120-kDa protein was consistently detected in cord extracts but not in platelet or VSMC homogenates. The immunohistochemistry study performed with the same antibody showed extensive cytoplasmic staining of VSMCs. The specific role of these different forms of platelet-type 12-lipoxygenase is subject to further investigation.
Alternative Splicing↗
Twist fields, the elliptic genus, and hidden symmetry.
We combine infinite dimensional analysis (in particular a priori estimates and twist positivity) with classical geometric structures, supersymmetry, and noncommutative geometry. We establish the existence of a family of examples of two-dimensional, twist quantum fields. We evaluate the elliptic genus in these examples. We demonstrate a hidden SL(2,Z) symmetry of the elliptic genus, as suggested by Witten.
Journal Article↗
Traumatic intracardiac thrombus.
Explore the source record for details and available documents.
Adult↗
Low-dose (1 microgram) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 microgram) test.
OBJECTIVE: We have shown previously that in contrast to the standard high-dose 250-microgram ACTH test, a low-dose 1-microgram ACTH stimulation test correctly identified all patients with pituitary disease who had impaired hypothalamo-pituitary-adrenal (HPA) function. In this study we further compared the performances of these two tests as screening procedures for possible HPA impairment. DESIGN: A comparison of the 1-microgram and the 250-microgram ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test. SUBJECTS: A total of 89 subjects were investigated: 27 healthy normal controls, 43 patients with pituitary disease and normal HPA function, and 19 patients with various pituitary diseases and impaired HPA function. MEASURES: All 89 subjects underwent stimulation with 1 microgram ACTH; 80 also underwent the high-dose 250-microgram ACTH test. A receiver operating characteristic analysis (ROC) was performed to compare the tests. RESULTS: Using a stimulated cortisol > 500 nmol/l as the criterion for a normal response, the 1-microgram ACTH stimulation identified 18 of the 19 subjects with impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6.2% sensitivity with a likelihood ratio of 0.875 for a negative test). All normal controls, and 36/43 patients with preserved HPA function, passed the 1-microgram ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered. CONCLUSIONS: More sensitive and accurate, the low-dose 1-microgram ACTH test is as simple and safe as the standard 250-microgram test. We suggest it should replace it in screening for adrenal insufficiency.
Adrenal Insufficiency↗
Contaminant eluted from solid-phase plasmid affinity-purification protocol columns is not found using liquid-phase methods and can be prevented.
The preparation of high quality plasmid DNA is a necessary requirement for most molecular biology applications. We compared four different large plasmid preparation protocols, which were based on either a liquid-phase approach (Triton lysis) or purification of alkaline lysis bacterial extracts followed by supercoiled plasmid purification on affinity columns. Two host Escherichia coli strains, JM 109 and INValphaF', were used to grow the test plasmids for comparison of product plasmid DNA produced from the four different plasmid isolation methods. While the DNA grown in E. coli strain JM109, prepared by liquid-phase Triton lysis was appropriately restricted by 12 restriction enzymes, this was not the case for any of the JM109-grown DNA purified by any of the affinity column solid-phase approaches. In contrast to this, when the plasmid DNA was grown in E. coli strain INValphaF', most restriction enzymes cut DNA appropriately, irregardless of the plasmid preparation protocol used. It seems that an impurity commonly eluted with the DNA from all three of the solid-phase DNA columns had an equal effect on the above enzymes using the common host strain JM109, but not strain INValphaF'.
Chromatography, Affinity↗
Pulmonary disease severity in men with deltaF508 cystic fibrosis and residual chloride secretion.
Explore the source record for details and available documents.
Adenosine Triphosphate↗
Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial.
BACKGROUND: We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial. METHODS: Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence. FINDINGS: Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p<0.05) degree of correction of the chloride abnormality in the patients receiving active treatment but not in those on placebo when assessed by in-vivo potential difference and chloride efflux. Bacterial adherence was also reduced. We detected no alterations in the sodium transport abnormality. A similar pattern occurred following nasal administration. INTERPRETATION: Cationic-lipid-mediated CFTR gene transfer can significantly influence the underlying chloride defect in the lungs of patients with cystic fibrosis.
Adult↗
Platelet-derived endothelial cell growth factor inhibits DNA synthesis in vascular smooth muscle cells.
Platelet-derived endothelial cell growth factor (PD-ECGF) is linked to angiogenesis in human cancer. Direct studies have demonstrated that PD-ECGF is a potent mitogen for endothelial cells in vivo. Because endothelial repair and smooth muscle cell proliferation are two processes that affect arterial wall structure and tone, we analyzed the effects of PD-ECGF on DNA synthesis and creatine kinase BB-specific activity (CK) in human umbilical artery smooth muscle cells (SMC) and in a human umbilical endothelial cell line (E304). In SMC, PD-ECGF (0.001 to 10 U/mL) inhibited DNA synthesis dose dependently (-24% + 6% to -63% + 15%) assessed by 3[H]thymidine incorporation into DNA, whereas in E304 it stimulated DNA synthesis dose dependently (30% + 4% to 100% + 4%). In both SMC and E304, however, PD-ECGF elicited an increase in CK-specific activity by 54% to 130% and 79% to 163%, respectively. These effects were reversed by a specific anti-PD-ECGF antibody. In E304 cells PD-ECGF enhanced 17beta-estradiol (E2) or dihydrotestosterone (DHT)-induced DNA synthesis from 56% to 122% and from 127% to 359%, and CK activity from 70% to 180% and from 90% to 190%, respectively. In SMC PD-ECGF, an inhibitor of 3[H]thymidine incorporation by itself, markedly enhanced the stimulatory effect of low concentrations of E2 and DHT on 3[H]thymidine incorporation. It also increased E2 and DHT CK induction from 40% to 140% and from 52% to 120%, respectively. In both E304 and SMC, PD-ECGF inhibited the proliferative and the CK-inducing effects of platelet-derived growth factor (PDGF) and immunoglobulin F1 (IGF1). Thus, PD-ECGF, an established growth promoter for endothelial cells, is a potent inhibitor of DNA synthesis in human arterial SMC. However, in both E304 endothelial cells and SMC, PD-ECGF enhances the stimulatory effect of low concentrations of gonadal steroids on 3[H]thymidine incorporation. PD-ECGF antagonizes PDGF- and IGF1-induced DNA synthesis in both E304 and SMC cells. By inhibiting arterial SMC proliferation and accelerating endothelial cell replication, PD-ECGF may buffer the effect of PDGF and favorably modulate arterial wall response to injury.
Cell Division↗
The in vivo effects of milrinone on the airways of cystic fibrosis mice and human subjects.
Previous studies have indicated that milrinone, a specific type III phosphodiesterase inhibitor, may be able to induce chloride secretion in cystic fibrosis (CF) tissues. We have now assessed the effect of this agent in vivo on the nasal epithelium of CF mutant mice and also in the nose and lungs of human subjects with CF. Wild-type mice showed a small hyperpolarization of the nasal potential difference (PD) in response to milrinone (100 microM, 1.6 +/- 0.6 mV, n = 8, P < 0.05). In contrast, CF mice carrying either the most common human mutation of the gene for the CF transmembrane regulator (CFTR), DeltaF508 (protein mislocalized), or the G551D mutation (protein normally localized) failed to demonstrate this response. Milrinone perfused alone had no significant effect on the baseline nasal PD of human subjects without CF (14.7 +/- 4.0 mV preperfusion; 15.3 +/- 4.6 mV postperfusion), but significantly (P < 0.05) augmented the hyperpolarization induced by a subsequently perfused low-chloride solution (with milrinone, 36.8 +/- 3.0 mV, n = 6; without milrinone, 18.1 +/- 2.2 mV, n = 19). In contrast, in human subjects with CF (n = 6), milrinone alone significantly (P < 0. 05) altered the nasal baseline PD (52.2 +/- 3.3 mV preperfusion; 57. 4 +/- 4.2 mV, postperfusion) but not the subsequent responses to the low-chloride solution (with milrinone, 1.1 +/- 2.2 mV, n = 4; without milrinone, 0.6 +/- 0.5 mV, n = 28) or to isoproterenol (100 microM). In a separate study in subjects (n = 6) with the DeltaF508 mutation, nasal coadministration of milrinone with isoproterenol produced no effect in the presence of amiloride and a low-chloride solution (-0.8 +/- 0.5 mV). This was also the case in the nasal epithelium of CF subjects (n = 4) carrying at least one G551D allele (-0.3 +/- 0.8 mV). Similarly, milrinone did not hyperpolarize the PD of either the tracheal (n = 6) or segmental (n = 6) airways of CF subjects (DeltaF508) when applied topically in vivo in the presence of amiloride, isoproterenol, or adenosine triphosphate (all 100 microM) in a low-chloride solution. These data do not support the use of milrinone to induce chloride secretion in CF airways in vivo.
Amiloride↗
Evaluating programs for recruiting and retaining community faculty.
BACKGROUND AND OBJECTIVES: There is a need to develop ambulatory care components within medical schools and, accordingly, a need to recruit community faculty. To assist in recruiting and retaining community faculty, this study addresses factors influencing physicians' decisions to serve as preceptors. The study also examines the relative value of incentives as rated by physicians in different primary care specialties. METHODS: We surveyed community physicians affiliated with a large, public teaching hospital. Physicians rated prior experiences training students in ambulatory settings, plans for serving as preceptors within the next year, and 7 incentives for serving as preceptors. RESULTS: A path analysis indicated that prior experiences and student influence on patient care affected future decisions to serve as preceptors. Analysis of the incentives for serving as preceptors indicated that physicians rated receiving continuing medical education (CME) credit the most favorably and financial compensation the least favorably. Overall, family physicians assigned the highest ratings to the incentives, and gynecologists gave the lowest ratings. CONCLUSIONS: This study produced a better understanding of the factors influencing physicians' decisions to serve as preceptors. Physicians are more concerned about students' influence on patient care than they are about students' influence on patient billings. In addition, preceptors preferred receiving nonmonetary compensation, such as CME credit, rather than receiving financial compensation. In addition, this study suggests better ways to reward community physicians for their service as preceptors. Community faculty should not be viewed as a homogenous group. The results of this study suggest that community physicians be provided with choices regarding the incentives for and rewards associated with serving as preceptors.
Ambulatory Care↗
In vivo expression of neutrophil inhibitory factor via gene transfer prevents lipopolysaccharide-induced lung neutrophil infiltration and injury by a beta2 integrin-dependent mechanism.
The binding of beta2 (CD18) integrins on PMN cell membrane to intercellular adhesion molecule (ICAM) counter-receptors on the surface of vascular endothelial cells mediates PMN adhesion to endothelial cells. Neutrophil inhibitory factor (NIF), a 41-kD glycoprotein isolated from the canine hookworm (Ancylostoma caninum), is a beta2 integrin antagonist that inhibits PMN adhesion to endothelial cells. We transferred the NIF gene into CD1 mouse lungs by intravenous injection of cationic liposomes to study the effects of in vivo NIF expression on LPS-induced lung PMN sequestration and the development of lung injury. RT-PCR and Northern blot analysis indicated the lung-selective expression of the NIF transgene, and immunocytochemistry showed prominent NIF expression in pulmonary microvessel endothelial cells. NIF staining was also observed in intraluminal leukocytes present in pulmonary microvessels. This may be the result of NIF binding to leukocytes after its secretion from the transduced lung cells, since there was no evidence of NIF gene expression in circulating leukocytes. Pulmonary vascular NIF expression abrogated the lung tissue PMN uptake and airspace migration of PMN and prevented lung vascular injury (as measured by the lung tissue uptake of [125I]labeled albumin) after the intraperitoneal LPS challenge (200 microg/mouse). Expression of a control protein, chloramphenicol acetyltransferase (CAT), by the same strategy, had no effect on these responses. In vitro studies showed that NIF prevented mouse PMN adhesion consistent with the inhibition of lung uptake after LPS challenge in NIF transgene-expressing mice. We conclude that pulmonary vascular expression of NIF, a specific beta2 integrin- binding protein, is a potentially useful gene transfer strategy in modulating the infiltration of PMN across the alveolar-capillary epithelial barrier and in preventing lung vascular endothelial injury.
Animals↗
Selections from current literature: minor depression.
The term "minor depression" has had several accepted definitions with differing diagnostic criteria. A review of papers published during the period 1991-1996, in which minor depression was a component of the study, demonstrates the extent of these differences. The heterogeneity of definitions of minor depression has been an obstacle to research on a mental disorder that appears to have a high prevalence and causes significant functional disability. As a result of these differing definitions, there is uncertainty about its natural history and prevalence, and whether therapy is beneficial. Agreement on a standard definition is necessary for investigations that are required to describe adequately these components of minor depression. This paper details the variety of definitions of minor depression and suggests use of the research diagnostic criteria published in the Diagnostic and Statistical Manual, fourth edition (DSM-IV) in future research.
Activities of Daily Living↗
Effects of gonadal steroids and their antagonists on DNA synthesis in human vascular cells.
The cardiovascular effect of estrogen is currently under intense investigation, but the role of androgens in vascular biology has attracted little attention. Because endothelial repair and vascular smooth muscle cell (VSMC) proliferation affect atherogenesis, we analyzed the effects of 17beta-estradiol (E2), dihydrotestosterone (DHT), and sex hormone antagonists on DNA synthesis in human umbilical VSMCs and in E304 cells (a human umbilical endothelial cell line). In VSMCs, both E2 and DHT had a biphasic effect on [3H]thymidine incorporation into DNA: low concentrations (0.3 nmol/L for E2, 3 nmol/L for DHT) stimulated [3H]thymidine incorporation (+35% and +41%, respectively), whereas high concentrations (30 nmol/L for E2, 300 nmol/L for DHT) inhibited [3H]thymidine incorporation (-40%). In contrast, E2 (0.3 to 300 nmol/L) and DHT (3 to 3000 nmol/L) dose-dependently enhanced [3H]thymidine incorporation in E304 cells (peak, +85% for both). In VSMCs, high concentrations of E2 and DHT inhibited platelet-derived growth factor (PDGF)-or insulin-like growth factor (IGF-1)-induced DNA synthesis (-50% to 80%), whereas PDGF- or IGF-1-dependent DNA synthesis in E304 cells was further increased by E2. The antiestrogens tamoxifen and raloxifene mimicked the effects of E2 on DNA synthesis in both VSMCs and E304 cells. However, when coincubated with a stimulatory concentration of E2 (0.3 nmol/L), tamoxifen and raloxifene blocked E2-induced [3H]thymidine incorporation in E304 cells but not in VSMCs. Finally, the androgen antagonist flutamide inhibited the biphasic effects of DHT on VSMCs and blocked the increase in DNA elicited by DHT in E304 cells. The results suggest complex, dose-dependent, and cell-specific interactions of estrogens, androgens, and their respective antagonists in the control of cellular proliferation in the vascular wall. Gonadal steroid-dependent inhibition of VSMC proliferation and stimulation of endothelial replication may contribute to vascular protection and remodeling responses to vascular injury.
Analysis of Variance↗
Comments on the comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease.
Explore the source record for details and available documents.
Adrenocorticotropic Hormone↗
The Escherichia coli histone-like protein HU affects DNA initiation, chromosome partitioning via MukB, and cell division via MinCDE.
Escherichia coli hupA hupB double mutants, lacking both subunits (HU1 and HU2) of the histone-like protein HU, accumulate secondary mutations. In some genetic backgrounds, these include mutations in the minCDE operon, inactivating this system of septation control and resulting in the formation of minicells. In the course of the characterization of hupA hupB mutants, we observed that the simultaneous absence of the HU2 subunit and the MukB protein, implicated in chromosome partitioning, is lethal for the bacteria; the integrity of either HU or MukB thus seems to be essential for bacterial growth. The HU protein has been shown to be involved in DNA replication in vitro; we show here that its inactivation in the hupA hupB double mutant disturbs the synchrony of replication initiation in vivo, as evaluated by flow cytometry. Our results suggest that global nucleoid structure, determined in part by the histone-like protein HU, plays a role in DNA replication initiation, in proper chromosome partitioning directed by the MukFEB proteins, and in correct septum placement directed by the MinCDE proteins.
Adenosine Triphosphatases↗
Role of the lipoxygenase pathway in angiotensin II-induced vasoconstriction in the human placenta.
We have previously shown that the vasopressor effect of angiotensin II (Ang II) is inhibited by lipoxygenase (LO) blockers. To elucidate the specific mechanism involved, we studied the relationship between the contractile effect of Ang II and LO products in a human placental preparation. In perfused placental cotyledons, Ang II (boluses of 1 to 10 microg) increased perfusion pressure and 12-hydroxyeicosatetraenoic acid (12-HETE) release. The LO blockers phenidone and n-propyl gallate reduced the maximal Ang II-induced increment in pressure from 26+/-3 to 16+/-3 and 18+/-4 mm Hg, respectively (P<.05 for both). Ang II alone (10 microg) increased 12-HETE release from 8.9+/-3.6 to 37.6+/-0.4 ng/min, and this rise was entirely blocked by both phenidone and n-propyl gallate. Pressure increase generated by an increase in flow rate had no effect on 12-HETE formation. In deendothelialized umbilical artery segments, Ang II (10(-7) mol/L) increased 12-HETE formation by 47+/-5% (n=20). In cultured umbilical artery smooth muscle cells, Ang II increased 12-HETE formation from 48.1+/-7.2 to 75.1+/-15.3 ng/mg protein, and this effect was also blocked by the specific LO inhibitor baicalein (10(-6) mol/L). These results provide evidence that the vasopressor effect of Ang II is functionally coupled to 12-LO activation, which apparently takes place in arterial smooth muscle cells.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗