Serving up food safety.
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Centers for Disease Control and Prevention, U.S.↗
Biomedical subjects
W Johnson
Publications and source records attributed to W Johnson.
Surveillance of invasive meningococcal disease in Canada, 1995-1996.
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Adolescent↗
Regulation of the human chorionic gonadotropin alpha- and beta-subunit promoters by AP-2.
Production of the placental hormone, chorionic gonadotropin (CG), increases dramatically as cytotrophoblasts fuse to form syncytiotrophoblasts. The CG alpha- and beta-promoters are both responsive to cAMP, although the kinetics of cAMP stimulation are different. In an effort to understand the mechanisms of coordinate induction of these genes, AP-2 binding sites were identified in the promoter regions of the alpha and CGbeta genes. AP-2 bound to the upstream regulatory element (-186 to -156 base pairs (bp)) in the alpha-promoter and to several different regions of the CGbeta promoter, including footprints 2 and 4B (FP2, -311 to -279 bp; FP4B, 221 to -200 bp). AP-2 antibodies induced supershifts of these complexes, confirming the identity of the protein-DNA complex. In JEG-3 cells, which contain abundant AP-2, mutations in these CGbeta AP-2 sites reduced basal activity and decreased cAMP stimulation. In AP-2-deficient Hep-G2 cells, co-transfection of AP-2 stimulated expression of the CGbeta promoter 10-20-fold, and the alpha-promoter was induced by 3-6-fold. Mutations that eliminate AP-2 binding to CGbeta FP4B reduced AP-2 stimulation by more than 80%, whereas mutations in FP2 reduced AP-2 stimulation by less than 50%. Analyses of AP-2 mutants revealed a requirement for the DNA binding/dimerization domain and the amino-terminal proline-rich and acid-rich transactivation domains for stimulation of the CGbeta promoter. Primary cultures of placental cytotrophoblasts were differentiated into syncytiotrophoblasts in vitro to examine AP-2 expression by reverse transcriptase-polymerase chain reaction. AP-2 mRNA levels increased by day 2 and continued to rise in parallel with a marked increase in alpha and CGbeta gene expression. We conclude that both the alpha and CGbeta promoters contain binding sites for AP-2 and suggest that this transcription factor provides a mechanism for coordinating the induction of these genes during placental cell differentiation.
Cell Nucleus↗
The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells.
The effects of the flavonoids quercetin, myricetin and silymarin on DNA damage and cytotoxicity in human cells were investigated. DNA strand breaks and oxidised pyrimidines were determined using alkaline single cell gel electrophoresis (the comet assay). Inhibition of cell growth was also measured. Caco-2 (colon), HepG2 (liver), HeLa (epithelial) cells and normal human lymphocytes showed different, dose-dependent susceptibilities (in terms of strand breakage) to the various flavonoids, quercetin being the most damaging. This agreed well with the ability of the flavonoids to inhibit cell growth. None of the flavonoids induced DNA base oxidation above background levels. All of the flavonoids under investigation caused depletion of reduced glutathione, which, in the case of quercetin, occurred prior to cell death. Neither cytotoxicity nor genotoxicity was associated with the antioxidant enzyme capacity (glutathione, glutathione reductase, glutathione peroxidase and catalase) of the cells.
Adenocarcinoma↗
Cardiovascular effects of different infusion rates of sufentanil in patients undergoing coronary surgery.
OBJECTIVE: Pharmacokinetics and haemodynamic effects of a total dose of 15 micrograms.kg-1 sufentanil, an opioid anaesthetic agent, were studied in patients undergoing aortocoronary bypass surgery at three infusion rates of 30 (group I), 5 (group II), and 2 (group III) micrograms.kg-1.min-1, respectively. RESULTS: Plasma concentrations of sufentanil could be optimally characterized by a linear biexponential pharmacokinetic model. Non-compartmental analyses indicated that there was no significant difference in the values of clearance (11.6, 13.3, 14.3 ml.min-1.kg-1), steady-state volume of distribution (0.220, 0.255 and 0.331 l.kg-1) and mean residence time (18.8, 13.3 and 14.3 min) among the groups. The observed mean Cmax values of 421 (group I), 125 (group II), and 53 (group III) ng.ml-1 and observed mean AUC values from 0 to 3 min were all consistent with the dosing regimens. There were large inter-individual variations in haemo-dynamic response. Compared to plasma data, a delay in haemodynamic effects was found. Times to reach peak haemodynamic effect ranged from 4.3 to 4.9 min for group I, from 4.6 to 6.1 min for group II, and from 9.9 to 11.3 for group III. Except heart rate, peak haemodynamic effects in these study patients generally ranged from 20.9% to 35.2%. Significant reductions in the area under the effect-time profiles of mean arterial blood pressure and systemic vascular resistance were observed in group II and group III, but not in group I. Significant reductions in the area under the effect-time profiles of left ventricular stroke work index were observed in group III only. No effect on heart rate was found in any group. CONCLUSION: Our findings suggested that a slower infusion rate of sufentanil at a dose of 15 micrograms.kg-1 tends to give a greater reduction in mean arterial blood pressure, systemic vascular resistance, and left ventricular stroke work index than does a faster infusion rate.
Analgesics, Opioid↗
Baker's cysts mimicking the symptoms of deep vein thrombosis: diagnosis with venous duplex scanning.
PURPOSE: The purpose of this study was to determine the incidence and characteristics of Baker's cysts discovered during venous duplex examinations to rule out deep vein thrombosis (DVT). METHODS: We reviewed the vascular laboratory charts of patients found to have Baker's cysts during venous duplex studies to rule out DVT from October 1988 through December 1995. RESULTS: Ninety-five (3.1%) of 3072 patients who underwent venous duplex studies were found to have 111 Baker's cysts. Seven of the 95 had coexistent DVT. Ten patients had ruptured cysts, whereas six patients had cysts that compressed the popliteal vein. CONCLUSION: The presentation of DVT and that of a Baker's cyst are similar enough to be difficult to distinguish by clinical examination. Careful examination of the popliteal fossa should be performed during venous duplex examinations regardless of the indication for the study.
Adult↗
Proteolipid protein is necessary in peripheral as well as central myelin.
Alternative products of the proteolipid protein gene (PLP), proteolipid protein (PLP) and DM20, are major components of compact myelin in the central nervous system, but quantitatively minor constituents of Schwann cells. A family with a null allele of PLP has a less severe CNS phenotype than those with other types of PLP mutations. Moreover, individuals with PLP null mutations have a demyelinating peripheral neuropathy, not seen with other PLP mutations of humans or animals. Direct analysis of normal peripheral nerve demonstrates that PLP is localized to compact myelin. This and the clinical and pathologic observations of the PLP null phenotype indicate that PLP/DM20 is necessary for proper myelin function both in the central and peripheral nervous systems.
Adolescent↗
Prevalence of anaerobes referred to the Canadian National Reference Centre from 1984 to 1996.
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Bacteria, Anaerobic↗
Soldier performance and strenuous road marching: influence of load mass and load distribution.
Fifteen male soldiers performed six maximal-effort, 20-km road marchers. They carried load masses of 34, 48, and 61 kg, using a standard military backpack with frame or an experimental doublepack. March times decreased as mass increased and were faster with the standard pack than with the double-pack. The doublepack resulted in less low back discomfort and a lower incidence of blisters at the highest load, but also resulted in more discomfort in the neck and hips. Neither load mass nor pack type affected soldiers' marksmanship ability, grenade throw accuracy, or cognitive ability. The maximal-effort march itself affected the marksmanship tasks by increasing the post-march vertical shot group dispersion. The concept of distributing the load mass more evenly around the center of mass of the body has both positive and negative aspects and warrants further investigation.
Blister↗
A coordinated high-performance liquid chromatographic, capillary electrophoretic, and mass spectrometric approach for the analysis of oligosaccharide mixtures derivatized with 2-aminoacridone.
Glycans derivatized with 2-aminoacridone have been analyzed consecutively by reverse-phase high-performance liquid chromatography (HPLC) and micellar electrokinetic capillary chromatography (MECC). The 2-aminoacridone derivatizing agent used in the present study is highly hydrophobic and is well separated from the glycan derivatives in both separation techniques, ensuring that excess reagent does not interfere with the oligosaccharide analysis. The methodology outlined uses the high resolving power of capillary electrophoresis to determine the heterogeneity of samples after collection and preconcentration by HPLC. Collected glycan samples are submitted for mass spectrometric analysis to determine molecular weight. This methodology has been applied to linear oligosaccharides derived from dextran and to N-linked mannose-rich glycans from ribonuclease B.
Aminoacridines↗
Effects of caloric restriction on expression of testicular cytochrome P450 enzymes associated with the metabolic activation of carcinogens.
Previous work demonstrated that microsomal cytochrome P4502A1 (CYP2A1) is expressed in rat testicular Leydig cells. The present study investigates the effects of diet, age, and strain on rat testicular CYP2A1 expression and assesses the potential role of testicular CYP2A1 in the metabolic activation of carcinogens. In ad libitum-fed 18-week-old Fischer 344 rats, testicular CYP2A1 immunoreactive protein and testosterone 7alpha-hydroxylase activity (7alpha-TOHase) exhibited a circadian variation with a daytime maximum and a night-time minimum (82.2 +/- 42.0 and 21.9 +/- 4.5 pmol 7alpha-hydroxytestosterone/min/mg protein, respectively). Caloric restriction (to 60% of ad libitum consumption), which reduces the severity of Leydig cell tumors in rats, decreased expression of both CYP2A1 and testicular 7alpha-TOHase >80% and eliminated their circadian variation. Conversely, caloric restriction induced a circadian rhythm in testicular 7-benzyloxyresorufin-O-dealkylase activity. Testicular microsomes from ad libitum-fed rats having peak diurnal 7alpha-TOHase activity had significantly greater (30%) microsome-mediated aflatoxin B1-DNA binding activity compared to microsomes prepared from nocturnal phase ad libitum-fed or calorically restricted rats which expressed low 7alpha-TOHase activity. In 12-month-old Fischer 344 rats, high CYP2A1 expression was correlated with severe Leydig cell hyperplasia (r = 0.80), whereas CYP2A immunoreactive protein and 7alpha-TOHase were expressed at lower levels in Sprague-Dawley than in Fischer 344 rats and were undetectable in pig, monkey, and human testes. These are strains/species that do not exhibit significant Leydig cell hyperplasia. This suggests that caloric intake, strain, and circadian factors may all mediate testicular CYP2A1 expression in the rat and that CYP2A1 may in turn influence carcinogen activation and pathological status in the testis.
Aflatoxin B1↗
Construction and characterization of human chromosome 2-specific cosmid, fosmid, and PAC clone libraries.
Three human chromosome 2-specific clone libraries were constructed and characterized. Chromosome 2-specific cosmid and fosmid clone libraries were constructed using flow-sorted DNA from the monochromosomal hybrid cell line GM10826. The cosmid and fosmid libraries consist of 38,496 and 26,400 arrayed clones, respectively, with an average size of 40 kb. Colony hybridization of a representative number of clones with both human and hamster genomic DNA probes demonstrates that between 58 and 66% of the clones in the flow-sorted libraries contain human inserts. Approximately 5% of the cosmid and fosmid clones are nonrecombinants. A chromosome 2-specific PAC library was also produced from the hybrid cell line GM10826. DNA from the hybrid cell line was cloned, and the human chromosome 2-specific clones were identified by colony hybridization. Approximately 5800 chromosome 2-specific PAC clones with an average insert size of approximately 85 kb were arrayed. Based on the size of the clones, the cosmid, fosmid, and PAC libraries are approximately 3.6x, approximately 2.5x, and approximately 1.9x, respectively in chromosomal coverage. The chromosome 2 coverage of each of the three libraries was further determined by PCR screening clone pools with 82 chromosome 2-specific STSs. The average number of clones identified for each STS in the library indicates the cosmid, fosmid, and PAC libraries to be approximately 3.2x, approximately 2.1x, and approximately 1.5x, respectively, in chromosome coverage. All except one of the 82 STSs were represented in the portions of the libraries screened.
Animals↗
Kinetic analysis of glutamate transport by the miniswine choroid plexus in vitro.
Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, was investigated by using the isolated choroid plexi from the fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of incubation with 1 microM glutamic acid. Tissue/medium ratios reached steady state by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory in a concentration-dependent manner, suggesting that it shares a common transport system, whereas neither octanoic acid nor okadaic acid (transported by a separate fatty acid system) inhibited glutamic acid transport. At the same temperature, the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%, and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The estimated Km values for glutamate uptake by the choroid plexus are 264 microM (FVCP) and 196 microM (LVCP); Vmax values are 87 (FVCP) and 147 (LVCP) nmol/g/min, respectively. These results indicate that, in addition to the metabolism of glutamate to glutamine, an active uptake mechanism is present in the choroid plexus of miniswine which may serve to regulate glutamic acid concentration in the CSF.
Animals↗
Acute cardiovascular effects of OPC-18790 in patients with congestive heart failure. Time- and dose-dependence analysis based on pressure-volume relations.
BACKGROUND: OPC-18790 is a water-soluble quinolinone derivative that shares the pharmacological properties of vesnarinone and that may be useful for treating heart failure. We studied the contribution and relative dose sensitivities of the inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated cardiomyopathy. METHODS AND RESULTS: Pressure-volume (PV) analysis was performed in 17 patients who received either 5 micrograms.kg-1.min-1 (low dose, n = 10) or 10 micrograms.kg-1.min-1 (high dose, n = 7) OPC-18790 by 1-hour IV infusion. Right heart pressures and flow and left heart PV relations (conductance catheter) were measured at baseline and every 15 minutes during infusion. Transient inferior vena caval obstruction was used to determine PV relations. Both doses produced venodilation reflected by a 10% decline in left ventricular end-diastolic volume and a 30% fall in atrial and pulmonary artery pressures. Arterial dilation was four times greater at the high dose, with an approximately 40% fall in effective arterial elastance and systemic resistance. Contractility rose by 25% to 100% (depending on PV index) with both doses. Ventricular-arterial coupling (ratio of ventricular end-systolic to arterial elastances) was approximately 0.25 at baseline and doubled (or tripled) at low (or high) dose, correlating with improved efficiency. Isovolumetric relaxation shortened, whereas the diastolic PV relation was generally unchanged. Heart rate was unaltered. CONCLUSIONS: OPC-18790 has potent venous and arterial vasodilator effects and moderate inotropic and lusitropic effects without a change in heart rate. These combined actions suggest a unique potential of OPC-18790 for heart failure treatment.
Blood Pressure↗
Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide bead-bound combinatorial libraries.
Electrospray, matrix-assisted laser desorption, and time-of-flight secondary ion mass spectrometry have been explored as possible methods for the identification of active members of molecular combinatorial libraries. All three methods are found to yield accurate molecular weight information about a target molecule angiotensin II antagonist synthesized on a 40-microns polystyrene bead. Structural identification is also possible by accurate mass measurements to eliminate candidate structures with the same nominal mass and by analysis of the fragmentation patterns. In addition, the secondary ion mass spectrometry measurements yield spatially resolved spectra from a single bead after exposure to a suitable gas which clips the covalent bond at the linking position. All three approaches appear to offer a viable screening strategy of non-peptide libraries without the use of additional molecular tags.
Angiotensin II↗
Laparoscopic fundoplication 1 month prior to lung transplantation.
Upper midline laparotomy in the presence of pulmonary failure is often complicated by a prolonged period of mechanical ventilation postoperatively. We report the successful performance of laparoscopic fundoplication, without ventilatory support, in a woman with end stage pulmonary disease and resting hypercarbia, one month prior to lung transplantation.
Female↗
Role of venous duplex scanning in patients with suspected pulmonary embolism.
PURPOSE: We examined the use of venous duplex scanning (VDS) in the diagnosis of pulmonary embolism (PE) at our institution. METHODS: Patients undergoing lower extremity VDS from October 1988 through June 1995 were cross-referenced with those who underwent ventilation perfusion (V/Q) scans and pulmonary angiography (PA) for PE. RESULTS: A total of 664 of 3534 VDS were for "rule out PE." Deep venous thrombosis was found in 13%. A total of 256 VDS were in conjunction with V/Q scans in 249 patients, with only 8% undergoing PA. Deep venous thrombosis was present in 18% for those with both V/Q and VDS compared with 10% (p < 0.01) for those with VDS as the sole study. The order in which V/Q, VDS, and PA were obtained and the relationship of positive studies was examined. CONCLUSION: We found no pattern to the sequence of tests ordered. V/Q scan rather than VDS should be the first study in the evaluation of PE. PE was diagnosed or excluded in nearly one third of patients based on V/Q as the initial study. A total of 29% of VDS could have been avoided. Treatment could be determined on the basis of VDS as the initial study in only 13%. We found only 14% incidence of positive PA in patients with nondiagnostic V/Q scans. We advocate judicious use of diagnostic tests in a stepwise fashion to appropriately treat patients with suspected PE.
Algorithms↗
Examination of external apical root resorption with scanning electron microscopy.
UNLABELLED: External apical root resorption may be evident histologically but not visible radiographically until it is advanced. If working length is determined without considering this resorption, overinstrumentation or overfilling may occur. OBJECTIVE: This study used scanning electron microscopy to examine the appearance and to compare the incidence of external apical root resorption in 40 teeth with differing pulpal and periapical diagnoses. STUDY DESIGN: After extraction, 46 roots were sectioned horizontally 6 mm from the anatomic apex and prepared for scanning electron microscopy examination. Photomicrographs were scored by two blinded independent examiners. Apical resorption was categorized as: none, partial, or complete. Presence or absence of a funneling appearance of the resorption was also recorded. RESULTS: Kruskal Wallis showed a significant difference in resorption between groups; teeth with irreversible pulpitis/normal periapex had the least resorption. Duncan's multiple range test found radiographic apical lesions to have more resorption than those without lesions; teeth with necrotic pulps had more resorption than those with vital pulps. CONCLUSION: Pulp necrosis with radiolucent apical pathosis is more likely to demonstrate resorption.
Chi-Square Distribution↗