Retention of drugs in venous access port chamber. Cause of drugs' effect is not clear.
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Anesthetics↗
Biomedical subjects
T Cook
Publications and source records attributed to T Cook.
Identification and characterization of zinc finger encoding genes from the tumoral exocrine pancreatic cell line AR42J.
Zinc finger transcription factors are DNA-binding proteins that are known to determine the identity of cells by regulating cell-specific gene expression. In addition, mutations in some members of this family have been found to be associated with several neoplasias, including Wilms' tumor and leukemias. Because the mechanisms that regulate normal, as well as neoplastic, pancreatic cell differentiation are poorly understood, we are searching for pancreas-enriched transcription factors that may determine the identity of pancreatic cells. Towards this end, we have used the polymerase chain reaction and degenerate primers against the highly conserved (Cys2-His2) zinc finger domain to amplify novel transcription factor encoding cDNAs from the well-characterized pancreatic acinar cell line AR42J. Using this approach, we have identified 17 different zinc finger encoding cDNAs (AZF-1 to -17). Sequence analysis shows that all of these clones encode for different zinc finger peptides which share the consensus DNA binding motif with the Drosophila transcription factor krüppel. As a first step in the characterization of these genes, the purified PCR products were used to determine their spatial pattern of expression by northern blot analysis. Using these techniques, we find that numerous zinc finger encoding genes are expressed in AR42J acinar cells as well as in normal adult rat pancreas and suggest that they may play a role as transcription factors in exocrine pancreatic cells.
Age Factors↗
Expression of dynamin immunoreactivity in experimental pancreatic tumors induced in rat by mancozeb-nitrosomethylurea.
Dynamins are GTPases which support receptor-mediated endocytosis and bind to several tyrosine kinase receptor-associated proteins known to mediate cell proliferation and differentiation. We have recently established that dynamin expression correlates with normal neuronal (Torre et al., J. Biol. Chem., 269 (1994) 32411-32417) and acinar pancreatic cell differentiation (Cook et al., Mol. Biol. Cell, 6 (1995) 405a). To begin to understand the role of dynamin in neoplastic pancreatic cell differentiation, we have followed the expression of this protein by immunohistochemistry during the development of pancreatic tumors in a mancozeb-nitrosomethylurea (NMU)-based carcinogenesis model recently developed in our laboratory (Monis and Valentich, Carcinogenesis, 14 (1993) 929-933). After a single intraperitoneal injection (50 mg/g body wt) of this carcinogen, rats fed with mancozeb develop pancreatic focal acinar hyperplasia (FACH), dysplastic foci (DYF) displaying acinar-like and ductular-like structures, and ductular-like carcinoma in situ (CIS). After histochemical staining using a monoclonal anti-dynamin antibody, high levels of this protein are consistently observed in well-differentiated acinar tumors (FACH). In contrast, dynamin immunoreactivity is almost undetectable in more advanced lesions showing a ductular-like phenotype (ductular-like DYF and CIS). This change in the expression pattern of dynamin during the progression of acinar into ductular-like DYF and CIS lesions correlates with recent findings from our laboratory showing a differential expression pattern for dynamin in pancreatic cells during embryonic development, with ductular-like precursor cells expressing low levels of this protein. Based upon these results, we conclude that more advanced ductular-like neoplastic cells induced by the carcinogen NMU in rat pancreas behave phenotypically like pancreatic precursor cells in their pattern of expression for dynamin.
Animals↗
Calcium-dependent interaction of N-type calcium channels with the synaptic core complex.
Neurotransmitter release is initiated by influx of Ca2+ through voltage-gated Ca2+ channels, within 200 microseconds of the action potential arriving at the synaptic terminal, as the Ca2+ concentration increases from 100 nM to > 200 microM. Exocytosis requires high Ca2+ concentration, with a threshold of 20-50 microM and half-maximal activation at 190 microM. The synaptic membrane proteins syntaxin, 25K synaptosome-associated protein (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin, are thought to form a synaptic core complex which mediates vesicle docking and membrane fusion. Synaptotagmin may be the low-affinity Ca(2+)-sensor, but other Ca(2+)-sensors are involved as residual neurotransmission persists in synaptotagmin-null mutants. Syntaxin binds to N-type Ca2+ channels at a site in the intracellular loop connecting domains II and III. Here we describe Ca(2+)-dependent interaction of this site with syntaxin and SNAP25 which has a biphasic dependence on Ca2+, with maximal binding at 20 microM free Ca2+, near the threshold for transmitter release. Ca(2+)-dependent interaction of Ca2+ channels with the synaptic core complex may be important for Ca(2+)-dependent docking and fusion of synaptic vesicles.
Animals↗
Three dynamin-encoding genes are differentially expressed in developing rat brain.
Dynamin proteins are members of a recently described family of GTPases involved in receptor-mediated processes. To date, three different dynamin-encoding genes have been identified in mammalian tissues. Dynamin I is expressed only in neurons, whereas dynamin II is ubiquitously expressed. A third isoform, dynamin III, was originally isolated from a rat testis cDNA library and shown to be testis-specific. However, here we report the cloning and characterization of dynamin III from brain and lung, demonstrating a more extended pattern of expression for this isoform. In addition, we have investigated the temporal pattern of expression of these three genes during brain development. We find that both dynamin I and dynamin III mRNA levels are up-regulated during embryogenesis, whereas dynamin II mRNA levels remain unchanged. From these results, we conclude that dynamin III is not a testis-specific isoform and, furthermore, that rat brain expresses three different dynamin-encoding genes that are differentially regulated during development. Therefore, this large isoform diversity of dynamin proteins in brain predicts a significant complexity in the understanding of dynamin-based processes in this tissue.
Alternative Splicing↗
Bronchodilatation and the inspiratory flow volume curve.
The inspiratory flow volume curve is included in the spirometric tracing provided by most pulmonary function laboratories and is useful in assessing upper airway abnormalities. We analyzed the changes in peak inspiratory flow (PIF), forced inspiratory flow at 50% (FIF50), and forced inspiratory vital capacity (FIVC) that occur with bronchodilator challenge testing (3 puffs of a beta-agonist by metered-dose inhaler without a spacer device) in 145 consecutive patients. Fifty-five patients responded to bronchodilators with either a 12% or 200-mL change in FEV1 or FVC. All of these subjects produced forced expiratory maneuvers that fulfilled American Thoracic Society criteria or acceptability. The FIVC was the only inspiratory parameter that consistently showed a similar correlation to the bronchodilator responsiveness demonstrated by the FEV1 or FVC. With the reduction in air trapping, a 12% or 200-mL change in the FIVC is additional confirmatory evidence of bronchodilator responsiveness.
Adrenergic beta-Agonists↗
Thomsen-Friedenreich and PK antigens in pig-to-human xenotransplantation.
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Animals↗
Workers' comp reimbursement in PA.
Workers' compensation reimbursement for providers has dramatically changed in the last five years with the passage of Act 44 in 1993 and Act 57 in 1996. Those new laws create forms, requirements, and prerequisites to payment. In November in five locations across the state, the State Society will sponsor one-day seminars on workers' compensation reimbursement. In this issue we begin a series of three articles on this topic, using some questions and answers posed by doctors and their staff. The articles supplement the Society's "Step-By-Step Guide to Workers' Compensation Reimbursement," to be published in conjunction with the seminars.
Humans↗
Increase your workers' comp billing recovery.
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Humans↗
A nurse practitioner-led, collaborative, outpatient practice: a case study in outcomes management.
To survive, a nurse practitioner-led primary care service must demonstrate that clinical care, patient satisfaction, and financial results are better than those of the competition. Nurse managers must develop a customer-oriented outcomes-management system to ensure the viability of the practice, especially in today's managed care environment. The authors describe how one nurse practitioner-led practice confronted these challenges to establish a successful business and provide opportunities for teaching and research.
Community Health Centers↗
Workers' comp reimbursement: commonly asked questions.
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Humans↗
Inhibition of the pig to human xenograft reaction, using soluble Gal alpha 1-3Gal and Gal alpha 1-3Gal beta 1-4GlcNAc.
Natural anti-carbohydrate antibodies are central to hyperacute rejection in ABO-incompatible allotransplantation and in discordant xenotransplantation. ABO-incompatible rejection has been inhibited successfully using intravenous soluble carbohydrates as antibody inhibitors. The approach has been less successful previously in pig to primate xenotransplantation, where the necessary concentrations of a partial inhibitor (Gal alpha 1-6Glc) proved highly toxic. In this study, we have identified more effective inhibitors of the dominant human anti-pig antibodies that bind to the pentasaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-. The inhibitors are the terminal disaccharide (Gal alpha 1-3Gal) and terminal trisaccharide (Gal alpha 1-3Gal beta 1-4GlcNAc) of the target pentasaccharide. Twelve sera (3 from each ABO blood group) were tested in 3 different assays: lymphocytotoxic, lymphocyte flow cytometry, and solid-phase antigen ELISA. Fifty percent to 75% inhibition of human IgG and IgM was achieved using the disaccharide and trisaccharide inhibitors in the range of 10-50 mM. Disaccharide (70 mM) was used to inhibit hyperacute thrombosis in pig kidneys perfused for 40 min with heparinized human AB whole blood. The disaccharide completely inhibited red cell occlusion of glomerular but not of intertubular capillaries, although there was residual platelet thrombus in glomeruli. Disaccharide and trisaccharide can, therefore, be used in concentrations shown for other carbohydrate inhibitors to be nontoxic, for inhibition of hyperacute pig-to-human xenograft rejection. The inhibition is incomplete, however, and other antigen specificities and other rejection mechanisms are likely to be involved.
ABO Blood-Group System↗
Effects of cholesterol lowering on the progression of coronary atherosclerosis in women. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) substudy.
BACKGROUND: Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering. METHODS AND RESULTS: Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol < or = 130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by < 3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured "blindly" on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%, P = .031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%, P < .001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial. CONCLUSIONS: Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women.
Adult↗
Loads in the spinal structures during lifting: development of a three-dimensional comprehensive biomechanical model.
Epidemiological studies have shown that loads imposed on the human spine during daily living play a significant role in the onset of low back pain. The loads applied to the lumbar spine are shared by a number of structures: muscles; posterior elements, including facets and ligaments; and the disc of a ligamentous motion segment. In vivo, it is not practical to determine forces in these structures using experimental techniques. Biomechanical models, based on an optimization technique of electromyographic activities of the trunk muscles, have been proposed to predict forces in the load transmitting structures. The mathematical models reported in the literature are based on information collected from a wide variety of sources, of which the subject that takes part in the experiment is only one. The present study describes techniques developed in our laboratory to collect from the subjects themselves all the data needed for the formulation of a biomechanical model. The results demonstrated that back lifting with 0 N (no load), 90 N, and 180 N in the hands created maximum external flexion moments respectively of 109.6 Nm, 137.9 Nm, and 161.7 Nm, at the L3-4 disc level. The corresponding external axial compression forces on the disc were 469.5 N, 511.8 N, and 601.5 N. The predicted disc compression varied from 3.4 to 5.0 times the body weight. In comparison to the static lifting mode, the dynamic lifting task caused an increase in the disc compression force ranging from 15.8% to 39.4% depending on the load being lifted (e.g., 3256 N for the dynamic mode vs. 2516 N for the static mode when the subject lifted 90 N). The salient features of the entire protocol developed by the authors and the need for further improvements are also presented.
Adult↗
Giant cell reparative granuloma of the cricoid cartilage.
Giant cell reparative granuloma (GCRG) is an uncommon benign lesion which has been reported at several sites in the head and neck. We present a case of a GCRG of the cricoid cartilage not previously described in the literature. It must be differentiated from the brown tumour of hyperparathyroidism and true giant cell tumours of bone. These were excluded on clinical, biochemical, radiological and histological grounds. The lesion responded well to surgical debulking and curettage and the patient remained disease-free 15 months after treatment.
Cricoid Cartilage↗
Intra- and inter-subject variabilities of CGP 33101 after replicate single oral doses of two 200-mg tablets and 400-mg suspension.
PURPOSE: The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subject variance to the overall variability. METHODS: Sixteen healthy subjects were randomly assigned to four groups to receive tablets and suspension twice in four different treatment sequences. The plasma concentration-time profile of CGP 33101 was characterized in terms of Cmax, Tmax, and AUC. Bioavailability of tablets relative to suspension and intra- and inter-subject variability were assessed by statistical analysis. RESULTS AND CONCLUSIONS: The overall variabilities in absorption kinetics of CGP 33101 in healthy subjects were small with CV's of the population mean values for AUC and Cmax less than 26% for both tablets and suspension. Contribution of intra-subject variability to the overall variability was also small (approximately 20%). Both the overall and intra-subject variabilities of AUC and Cmax after suspension were larger than after the tablets. However, the differences in variability between tablets and suspension were not statistically significant (p > 0.05). The tablet formulation was bioequivalent to suspension in terms of rate and extent of absorption based on 90% conventional confidence intervals (for AUC and Cmax) and Wilcoxon rank-sum test (for Tmax).
Administration, Oral↗
The nitric oxide pathway in glomerulonephritis.
Nitric oxide has fundamental roles in the modulation of many cell functions. In glomerulonephritis, generation of nitric oxide by the acutely inflamed glomerulus has recently been confirmed, with evidence that synthesis occurs through induction of the inducible form of nitric oxide synthase. Recent studies implicate infiltrating macrophages as a major source of this activity, although intrinsic glomerular cells may contribute as nitric oxide synthase has been found in cytokine-stimulated mesangial, endothelial and epithelial cells in culture. Cytokines, which are known to have a central role in glomerulonephritis, are the most probable stimulus of nitric oxide synthase induction in vivo, although this awaits confirmation. A role for nitric oxide in the pathophysiology of glomerulonephritis is not clearly defined at present but is strongly suggested by evidence for participation of nitric oxide in other immune and inflammatory diseases. The evidence evaluated in this review emphasizes that the role is certain to be complex. As yet it is not possible to predict whether the modulatory effects of nitric oxide on glomerular haemodynamics, vascular integrity, leucocyte infiltration and intrinsic glomerular cell responses are predominantly protective or cytotoxic. There are presently only two fully published reports of inhibition of nitric oxide in models of glomerulonephritis, one of which showed an exacerbation of acute heterologous nephrotoxic injury, and the other showed amelioration of chronic autoimmune glomerulonephritis. It is therefore premature to speculate on the effects of nitric oxide inhibition in glomerulonephritis. New insights await further understanding of the regulation of the inducible form of nitric oxide synthase in glomerulonephritis and the availability of specific inhibitors of this enzyme.
Animals↗
Pediatric asthma--a correlation of clinical treatment and oxygen saturation.
To determine the relationship between changes in room air oxygen saturation (SaO2) and changes in the clinical signs of pediatric asthma patients after treatment with nebulized albuterol, a 9-month prospective observational study was conducted. Eighty-two patients from 2 to 15 years of age who had exacerbations of asthma were studied when they presented to a military community hospital emergency department with an annual census of 62,500. For each patient, the change in SaO2 30 minutes after administration of nebulized albuterol was compared to the change in an ordinal clinical scoring system for asthma. Physicians were blinded to SaO2 measurements. Data are reported as mean values with differences between groups analyzed using the paired t-test. Patients with an initial SaO2 < 95% who clinically improved after treatment had a mean increase in their SaO2 of 2.6%. Patients with an initial SaO2 < 95% who did not clinically improve after treatment had a mean decrease in SaO2 of 1.1%, but this was not statistically significant (p = 0.14). The positive predictive value for improved SaO2 indicating clinical improvement is 98%. Patients with an initial SaO2 > 95% did not have significant changes in SaO2 after treatment regardless of clinical response. For pediatric asthma patients with an initial SaO2 < 95%, increased SaO2 after treatment with inhaled albuterol is predictive of clinical improvement. Patients with an initial SaO2 < 95% who do not have improved SaO2 after treatment require further evaluation.
Adolescent↗