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Biomedical subjects

M E Anderson

Publications and source records attributed to M E Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Autoprotection in acetaminophen intoxication in rats: the role of liver regeneration.

Autoprotection by acetaminophen, i.e. increased resistance to toxic effects caused by pretreatment, is a well-known phenomenon. The purpose of the present work was to identify mechanisms for increased acetaminophen tolerance induced by pretreatment of rats. One group of female Wistar rats (pretreated rats) received acetaminophen orally in increasing doses (1 to 4.3 g/kg) twice a week for 3 weeks, one group (naïve rats) received the vehicle. At time zero pretreated rats received a toxic dose of 7.5 g/kg (100% lethal in naïve rats), and naïve rats received a toxic dose of 4.3 g/kg. Blood and liver tissue were collected before and 12, 24, 36, and 48 hr after the toxic dose and were analysed for hepatic glutathione and cysteine contents, hepatic glutathione-S-transferase and blood alanine aminotransferase activity, as well as acetaminophen concentration in plasma. Steady-state mRNA levels of proteins involved in acetaminophen detoxification, cell division and acute phase response were measured, liver tissue was examined for proliferating cell nuclear antigen and degree of hepatocyte necrosis. Six naïve rats not receiving acetaminophen served as controls. The mortality was the same in pre-treated and naïve rats (33 percent). Thus, pretreatment increased the tolerance twice. Before the toxic dose pretreated rats compared to control rats had higher activity of glutathione-S-transferase (liver) and alanine aminotransferase (serum), higher hepatic mRNA level of glutathione-S-transferase and gamma-glutamylcysteine synthetase heavy and light chain subunits, and lower hepatic concentration of glutathione, cysteine and mRNA of CYP1A2 than control rats. After the toxic dose, the mRNA levels of glutathione-S-transferase, gamma-glutamylcysteine synthetase heavy and light chain subunits, and CYP1A2 in naïve rats rose, approaching those of pretreated rats. Proliferating cell nuclear antigen labelling was high in pretreated rats, while only slightly increased in a few of the naïve rats. Necrotic hepatocytes were found at all time intervals in pretreated rats, and in naïve rats they appeared after 12 hr, peaking after 36 hr. Pretreatment increased the tolerance to acetaminophen toxicity twice, as estimated by mortality. The data indicate that pretreatment may reduce the relative production of toxic metabolites, but it primarily enhances the protection against these metabolites by regenerating hepatocytes.

Acetaminophen↗
PubMed2001

Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis.

Juvenile polyposis (JP; OMIM 174900) is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. Previous studies have demonstrated a locus for JP mapping to 18q21.1 (ref. 3) and germline mutations in the homolog of the gene for mothers against decapentaplegic, Drosophila, (MADH4, also known as SMAD4) in several JP families. However, mutations in MADH4 are only present in a subset of JP cases, and although mutations in the gene for phosphatase and tensin homolog (PTEN) have been described in a few families, undefined genetic heterogeneity remains. Using a genome-wide screen in four JP kindreds without germline mutations in MADH4 or PTEN, we identified linkage with markers from chromosome 10q22-23 (maximum lod score of 4.74, straight theta=0.00). We found no recombinants using markers developed from the vicinity of the gene for bone morphogenetic protein receptor 1A (BMPR1A), a serine-threonine kinase type I receptor involved in bone morphogenetic protein (BMP) signaling. Genomic sequencing of BMPR1A in each of these JP kindreds disclosed germline nonsense mutations in all affected kindred members but not in normal control individuals. These findings indicate involvement of an additional gene in the transforming growth factor-beta (TGF-beta) superfamily in the genesis of JP, and document an unanticipated function for BMP in colonic epithelial growth control.

Adenomatous Polyposis Coli↗
PubMed2001

Functional similarity between electrograms recorded from an implantable cardioverter defibrillator emulator and the surface electrocardiogram.

Clinical use of stored electrogram (EGM) configurations currently used in ICDs is limited. The hypothesis that EGMs recorded from electrodes on the ICD surface may improve diagnostic capabilities of the device was tested in the present study. The Buttons on Active Can Emulator (BACE), an ICD-sized device containing four button electrodes, was temporarily placed into a subcutaneous or submuscular left pectoral pocket in 16 patients during ICD implantation. Simultaneous recordings were obtained from the ECG lead II, bipolar EGMs using BACE electrodes, and a bipolar atrial EGM during sinus rhythm (SR), ventricular pacing (VP) at cycle lengths of 500 and 400 ms, and VT. Visible P waves were present in all patients during SR (n = 15), in 5 (33%) of 15 patients during VP, and none of the patients during VT (n = 4) using BACE EGMs and lead II. P and QRS amplitudes and the P:QRS ratio during SR in BACE EGMs were significantly lower than those in lead II. BACE EGMs showed prominent changes in QRS morphology and duration during VP and VT compared to SR, and the magnitude of QRS prolongation during VP was similar to that in lead II. Measurements of PR, QRS, and QT duration during SR showed good agreement between BACE EGMs and lead II. In conclusion, EGMs recorded from electrodes embedded on the ICD housing may potentially improve visual discrimination between supraventricular and ventricular arrhythmias. They also may be useful as a surrogate of the ECG for analysis and monitoring of different components of P-QRS-T complex.

Defibrillators, Implantable↗
PubMed2001

2-D motion estimation using two parallel receive beams.

We describe a method for estimating 2-D target motion using ultrasound. The method is based on previous ensemble tracking techniques, which required at least four parallel receive beams and 2-D pattern matching. In contrast, the method described requires only two parallel receive beams and 1-D pattern matching. Two 1-D searches are performed, one in each lateral direction. The direction yielding the best match indicates the lateral direction of motion. Interpolation provides sub-pixel magnitude resolution. We compared the two beam method with the four beam method using a translating speckle target at three different parallel beam steering angles and transducer angles of 0, 45, and 90 degrees. The largest differences were found at 90 degrees, where the two beam method was generally more accurate and precise than the four beam method and also less prone to directional errors at small translations. We also examined the performance of both methods in a laminar flow phantom. Results indicated that the two beam method was more accurate in measuring the flow angle when the flow velocity was small. Computer simulations supported the experimental findings. The poorer performance of the four beam method was attributed to differences in correlation among the parallel beams. Specifically, center beams 2 and 3 correlated better with each other than with the outer beams. Because the four beam method used a comparison of a kernel region in beam pair 2-3 with two different beam pairs 1-2 and 3-4, the 2-to-1 and 3-to-4 components of this comparison increased the incidence of directional errors, especially at small translations. The two beam method used a comparison between only two beams and so was not subject to this source of error. Finally, the two beam method did not require amplitude normalization, as was necessary for the four beam method, when the two beams were chosen symmetric to the transmit axis. We conclude that two beam ensemble tracking can accurately estimate motion using only two parallel receive beams.

Biomedical Engineering↗
PubMed2001

A role for physician assistants in organ procurement.

Healthcare in the United States, as well as the environment in which physician assistants work, is rapidly changing. Consequently, the role of a physician assistant is expanding to meet the needs of patients and physicians of all specialties of medicine and surgery. In organ procurement, physician assistants can be a valuable asset to an organ procurement organization because of their medical education, versatility, and commitment to personalized care to organ donors and their families. Physician assistants are healthcare professionals who are uniquely qualified for a variety of roles within the organization: clinician, educator, consultant, donor and family liaison, and researcher.

Adult↗
PubMed2001

Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.

Quinolones are clinically important antibiotic drugs. One quinolone antibiotic, sparfloxacin (SPX), has been recently reported to increase the QT interval, and another quinolone, grepafloxacin (GRX), was withdrawn because it induced torsade de pointes (TdP), a polymorphic ventricular tachycardia (VT) linked to excessive QT interval prolongation. To determine whether SPX, GRX, and other recently developed quinolones, gatifloxacin (GAT) and moxifloxacin (MOX), have similar, potentially deleterious, properties we compared these agents in two ways. First, we measured their relative antagonist potency against the rapid component of the delayed rectifier K(+) current (I(Kr)), and second we determined the QT interval prolongation and inducibility of VT and TdP using a well established in vivo rabbit arrhythmia model. All of these agents are I(Kr) antagonists with the following IC(50) values (mean +/- S.E.) for I(Kr) block: SPX, 0.23 +/- 0.07 microM; MOX, 0.75 +/- 0.31 microM; GAT, 26.5 +/- 13.4 microM; and GRX, 27.2 +/- 11.6 microM. All agents also increased the maximum QT interval (mean +/- S.E.) from baseline (241 +/- 10 ms): SPX, 370 +/- 30 ms; MOX, 270 +/- 30 ms; GRX, 280 +/- 25 ms; and GAT, 255 +/- 23 ms. No agents caused TdP during a standard 30-min observation period, but SPX-treated animals developed nonsustained VT (three of six) and TdP (one of six) during an extended 60-min observation period. These findings show that I(Kr) block may be a common feature of many quinolone antibiotics, and that the proarrhythmic consequences vary according to I(Kr) antagonist potency, but are also influenced by additional, unidentified factors.

4-Quinolones↗
PubMed2000

Determinants for calmodulin binding on voltage-dependent Ca2+ channels.

Calmodulin, bound to the alpha(1) subunit of the cardiac L-type calcium channel, is required for calcium-dependent inactivation of this channel. Several laboratories have suggested that the site of interaction of calmodulin with the channel is an IQ-like motif in the carboxyl-terminal region of the alpha(1) subunit. Mutations in this IQ motif are linked to L-type Ca(2+) current (I(Ca)) facilitation and inactivation. IQ peptides from L, P/Q, N, and R channels all bind Ca(2+)calmodulin but not Ca(2+)-free calmodulin. Another peptide representing a carboxyl-terminal sequence found only in L-type channels (designated the CB domain) binds Ca(2+)calmodulin and enhances Ca(2+)-dependent I(Ca) facilitation in cardiac myocytes, suggesting the CB domain is functionally important. Calmodulin blocks the binding of an antibody specific for the CB sequence to the skeletal muscle L-type Ca(2+) channel, suggesting that this is a calmodulin binding site on the intact protein. The binding of the IQ and CB peptides to calmodulin appears to be competitive, signifying that the two sequences represent either independent or alternative binding sites for calmodulin rather than both sequences contributing to a single binding site.

Amino Acid Sequence↗
PubMed2000

Novel kinetics of mammalian glutathione synthetase: characterization of gamma-glutamyl substrate cooperative binding.

Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. Mammalian glutathione synthetase is a homodimer with each subunit containing an active site. We report the detailed kinetic data for purified recombinant rat glutathione synthetase. It has the highest specific activity (11 micromol/min/mg) reported for any mammalian glutathione synthetase. The apparent K(m) values for ATP and glycine are 37 and 913 microM, respectively. The Lineweaver-Burk double reciprocal plot for gamma-glutamyl substrate binding revealed a departure from linearity indicating cooperative binding. Quantitative analysis of the kinetic results for gamma-glutamyl substrate binding gives a Hill coefficient (h) of 0. 576, which shows the negative cooperativity. Neither ATP, the other substrate involved in forming the enzyme-bound gamma-glutamyl phosphate intermediate, nor glycine, which attacks this intermediate to form GSH, exhibit any cooperativity. The cooperative binding of gamma-glutamyl substrate is not affected by ATP concentration. Thus, mammalian glutathione synthetase is an allosteric enzyme.

Animals↗
PubMed2000

Binding of octa-plus porphyrazines to DNA.

We present a preliminary report of the interaction of octacationic N-methyl-pyridyl metalloporphyrazines, M=Cu(II) (Cupz+8) and Zn(II) (Znpz+8), with calf thymus DNA. These were monitored by electronic absorption spectroscopy, and in the case of Znpz+8, also by emission spectroscopy. These studies show that both the Cupz+8 and Znpz+8 interact strongly with DNA, and at sufficient concentrations induce a highly colored precipitate. The spectrum of Cupz+8 red-shifts as DNA is added, which is interpreted as indicative of pi stacking of the charged macrocycle as it binds electrostatically to the outside of the DNA duplex. The spectrum of Znpz+8 does not shift, indicative of simple electrostatic surface binding. The absence of stacking may be related to the presence of an axial metal-ion ligand for Znpz+8, presumably 1120, while the metal ion of Cupz+8 is four-coordinate.

Animals↗
PubMed2000

Bis(dimethylamino)porphyrazines: synthetic, structural, and spectroscopic investigations.

The synthesis and isolation of unsymmetrical porphyrazines bearing two, four, and six bis-(dimethylamino) functionalities has been achieved via the base-catalyzed cross-condensation of 1,2-dicyanobenzene 8 and bis(dimethylamino)maleonitrile 7. In addition, the benzo-fused hexaaminoporphyrazine dimer 10 was prepared from condensation of dinitrile 7 (in excess) with benzenebis(1,3-diiminopyrroline) 9. Electrochemical studies reveal that all porphyrazines may be readily oxidized. The X-ray structures of porphyrazines 2b and 5a and the cis isomer 3a are presented. The latter is the first structure of a porphyrazine having a cis-type substitution pattern. The extended pi-conjugation in dimer 10 causes a approximately 100 nm red-shifted Q-band in the electronic absorption spectrum.

Crystallography, X-Ray↗
PubMed2000

Ca2+-activated non-selective cation current in rabbit ventricular myocytes.

Oscillatory currents (OCs) were studied in isolated rabbit ventricular myocytes with whole cell mode voltage clamp using Na+-free intracellular and extracellular solutions under conditions where K+ currents were anticipated to be eliminated or minimized. All OCs were dependent on release of Ca2+ from the sarcoplasmic reticulum (SR) because they were associated with intracellular Ca2+ ([Ca2+]i) transients, and were suppressed by high concentrations of BAPTA (20 mmol l-1) or pretreatment with the SR antagonist agents ryanodine (10 micromol l-1) or thapsigargin (1 micromol l-1). The reversal potential (Vrev) for OCs shifted with changes in the calculated Vrev for Cl- (ECl) but was between ECl and the calculated Vrev for elemental monovalent cations (ECat), indicating that more than one Ca2+-activated current contributed to OCs. Addition of the Ca2+-activated Cl- current (ICl(Ca)) antagonist, niflumic acid, shifted the OC Vrev to ECat, suggesting that ICl(Ca) and a Ca2+-activated non-selective cation current (ICAN) contributed to the observed OCs. A reduced niflumic acid-insensitive Ca2+-activated OC persisted following marked symmetrical reduction of Cl- in the intracellular and extracellular solutions. Subsequent removal of all extracellular monovalent cations, by N-methyl-D-glucamine (NMDG) substitution, eliminated OCs and the inward holding current suggesting that ICAN and ICl(Ca) accounted for all or most of the Ca2+-activated OC in the absence of Na+. The OC Vrev was equal to ECl in the absence of monovalent elemental cations. Under these conditions niflumic acid eliminated all OCs. Macroscopic OC is partially due to ICAN in rabbit ventricular myocytes.

Animals↗
PubMed2000

Speckle tracking for multi-dimensional flow estimation.

Speckle tracking methods overcome the major limitations of current Doppler methods for flow imaging and quantification: angle dependence and aliasing. In this paper, we review the development of speckle tracking, with particular attention to the advantages and limitations of two-dimensional algorithms that use a single transducer aperture. Ensemble tracking, a recent speckle tracking method based upon parallel receive processing, is described. Experimental results with ensemble tracking indicate the ability to measure laminar flow in a phantom at a beam-vessel angle of 60 degrees, which had not been possible with previous 2D speckle tracking methods. Finally, important areas for future research in speckle tracking are briefly summarized.

Algorithms↗
PubMed2000

Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels.

A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for ICa facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent ICa facilitation.

Animals↗
PubMed2000

A novel interpolation strategy for estimating subsample speckle motion.

Multidimensional, high-resolution ultrasonic imaging of rapidly moving tissue is primarily limited by sparse sampling in the lateral dimension. In order to achieve acceptable spatial resolution and velocity quantization, interpolation of laterally sampled data is necessary. We present a novel method for estimating lateral subsample speckle motion and compare it with traditional interpolation methods. This method, called grid slopes, requires no a priori knowledge and can be applied to data with as few as two samples in the lateral dimension. Computer simulations were performed to compare grid slopes with two conventional interpolation schemes, parabolic fit and cubic spline. Results of computer simulations show that parabolic fit and cubic spline performed poorly at translations greater than 0.5 samples, and translations less than 0.5 samples were subject to an estimation bias. Grid slopes accurately estimated translations between 0 and 1 samples without estimation bias at high signal-to-noise ratios. Given that the grid slopes interpolation technique performs well at high signal-to-noise ratios, one pertinent clinical application might be tissue motion tracking.

Algorithms↗
PubMed2000

Enhancement of 2000-m rowing performance after caffeine ingestion.

PURPOSE: To investigate the effect of caffeine ingestion on short-term endurance performance in competitive rowers. METHODS: In this randomized double-blind crossover study, eight competitive oarsmen (peak oxygen uptake [VO2peak] 4.7+/-0.4 L x min(-1), mean +/- SD) performed three familiarization trials of a 2000-m rowing test on an air-braked ergometer, followed by three experimental trials at 3- to 7-d intervals, each 1 h after ingesting caffeine (6 or 9 mg x kg(-1) body mass) or placebo. Trials were preceded by a standardized warm-up (6 min at 225+/-39 W; 75+/-7.7% VO2peak). RESULTS: Urinary caffeine concentration was similar before ingestion (approximately 1 mg x L(-1)) but rose to 6.2+/-3.6 and 14.5+/-7.0 mg x L(-1) for the low and high caffeine doses, respectively. Plasma free fatty acid concentration before exercise was higher after caffeine ingestion (0.29+/-0.17 and 0.39+/-0.20 mM for 6 and 9 mg x kg(-1), respectively) than after placebo (0.13+/-0.05 mM). Respiratory exchange ratio during the warm-up was also substantially lower with caffeine (0.94+/-0.09 and 0.93+/-0.06 for the low and high dose) than with placebo (0.98+/-0.12). Subjects could not distinguish between treatments before or after the exercise test. Both doses of caffeine had a similar ergogenic effect relative to placebo: performance time decreased by a mean of 1.2% (95% likely range 0.4-1.9%); the corresponding increase in mean power was 2.7% (0.4-5.0%). Performance time showed some evidence of individual differences in the effect of caffeine (SD 0.9%; 95% likely range 1.5 to -0.9%). CONCLUSIONS: Ingestion of 6 or 9 mg x kg(-1) of caffeine produces a worthwhile enhancement of short-term endurance performance in a controlled laboratory setting.

Caffeine↗
PubMed2000

The impact of sound speed errors on medical ultrasound imaging.

The results of a quantitative study of the impact of sound speed errors on the spatial resolution and amplitude sensitivity of a commercial medical ultrasound scanner are presented in the context of their clinical significance. The beamforming parameters of the scanner were manipulated to produce sound speed errors ranging over +/-8% while imaging a wire target and an attenuating, speckle-generating phantom. For the wire target, these errors produced increases in lateral beam width of up to 320% and reductions in peak echo amplitude of up to 10.5 dB. In the speckle-generating phantom, these errors produced increases in speckle intensity correlation cell area of up to 92% and reductions in mean speckle brightness of up to 5.6 dB. These results are applied in statistical analyses of two detection tasks of clinical relevance. The first is of low contrast lesion detectability, predicting the changes in the correct decision probability as a function of lesion size, contrast, and sound speed error. The second is of point target detectability, predicting the changes in the correct decision probability as function of point target reflectivity and sound speed error. Representative results of these analyses are presented and their implications for clinical imaging are discussed. In general, sound speed errors have a more significant impact on point target detectability over lesion detectability by these analyses, producing up to a 22% reduction in correct decisions for a typical error.

Humans↗
PubMed2000

Improved 2000-meter rowing performance in competitive oarswomen after caffeine ingestion.

Eight competitive oarswomen (age, 22 +/- 3 years; mass, 64.4 +/- 3.8 kg) performed three simulated 2,000-m time trials on a rowing ergometer. The trials, which were preceded by a 24-hour dietary and training control and 72 hours of caffeine abstinence, were conducted 1 hour after ingesting caffeine (6 or 9 mg á kg-1 body mass) or placebo. Plasma free fatty acid concentrations before exercise were higher with caffeine than placebo (0.67 +/- 0.34 vs. 0.72 +/- 0.36 vs. 0.30 +/- 0.10 mM for 6 and 9 mg á kg-1 caffeine and placebo, respectively; p <.05). Performance time improved 0.7% (95% confidence interval [CI] 0 to 1.5%) with 6 mg á kg-1 caffeine and 1. 3% (95% CI 0.5 to 2.0%) with 9 mg á kg-1 caffeine. The first 500 m of the 2,000 m was faster with the higher caffeine dose compared with placebo or the lower dose (1.53 +/- 0.52 vs.1.55 +/- 0.62 and 1. 56 +/- 0.43 min; p =.02). We concluded that caffeine produces a worthwhile enhancement of performance in a controlled laboratory setting, primarily by improving the first 500 m of a 2,000-m row.

Adult↗