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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 217 records · Page 12Linked to original sources
PubMed1995

Effects of no flow and reperfusion on technetium-99m-Q12 kinetics.

UNLABELLED: The purpose of this study were to determine if 99mTc-Q12 tracer kinetics could be affected by the insult of total no flow followed by reflow and the effects of viability on clearance. METHODS: In six control buffer perfused rat hearts, flow was maintained at 12 ml/min throughout uptake and clearance. In six hearts (IR30), 30 min of no flow was followed by 60 min of reflow. In six hearts (IR60), 60 min of no flow was followed by 60 min of reflow. One millicurie 99mTc-Q12 was injected in control hearts or during reflow in the IR30 and IR60 hearts and myocardial clearance was monitored for 1 hr using a Nal detector. RESULTS: Control hearts demonstrated biphasic 99mTc-Q12 myocardial clearance with an early rapid clearance phase ending 5-10 min after injection (73.5% +/- 1.5% retention) followed by a late slow clearance phase (90.5% +/- 0.2% retention). IR30 hearts demonstrated a near identical clearance curve (74.3% +/- 0.9% early retention, 90.9% +/- 0.6% late retention). IR30 heart electron micrographs demonstrated predominantly ischemia insulted but viable cells. IR60 hearts also demonstrated a biphasic myocardial clearance, with a late slow phase similar to controls (91.9% +/- 0.6% retention). The early rapid phase was significantly faster than controls (61.1% +/- 3.4%). IR60 heart electron micrographs demonstrated predominantly injured nonviable cells. Well counting confirmed decreased retention in the IR60 rats compared to controls and IR30 rats. CONCLUSION: Technetium-99m-Q12 myocardial clearance is normally biphasic, with an early rapid phase ending after 5-10 min and a late slow phase. Ischemicaly insulted but viable myocardium created by 30 min of no flow followed by reflow has no effect on either clearance phase. This tracer warrants further study to determine its potential utility in assessing myocardial viability.

Animals↗
PubMed1995

Myocardial clearance kinetics of technetium-99m-teboroxime following dipyridamole: differentiation of stenosis severity in canine myocardium.

UNLABELLED: The purpose of the current study was to determine whether teboroxime clearance kinetics are useful in differentiating the severity of coronary artery flow restriction. METHODS: Groups of dogs received stenoses of the left circumflex coronary artery as follows: nine dogs received a mild-to-moderate stenosis (Group 2) and eleven dogs received severe stenoses (Group 3). In three control dogs (Group 1), there was no stenosis. Using miniature cadmium-telluride radiation detectors, myocardial teboroxime activities were continuously monitored in both the control and stenosed zones following dipyridamole infusion. RESULTS: A significant difference in fractional myocardial clearance between the control zones (0.69 +/- 0.01, n = 26) versus mild-to-moderate (0.61 +/- 0.06, p < 0.05, n = 9) and severe (0.57 +/- 0.03, p < 0.01 versus control, p < 0.05 versus mild-to-moderate, n = 11) flow-restricted zones was observed over a 1-hr period. Significant differences between normal and both stenosed zones became apparent after 7 min of clearance. Significant differences in myocardial clearance between mild-to-moderate and severe groups were detected within 15 min. CONCLUSION: Thus, in this canine model using dipyridamole, miniature probe-determined teboroxime myocardial clearance can differentiate among normal myocardium, myocardium distal to a mild-to-moderate stenosis and myocardium distal to a severe stenosis.

Animals↗
PubMed1994

Amphiregulin as an autocrine growth factor for c-Ha-ras- and c-erbB-2-transformed human mammary epithelial cells.

Amphiregulin (AR), a member of the epidermal growth factor (EGF) family, was found to be as potent as EGF in stimulating the anchorage-dependent growth (ADG) of immortalized, nontransformed human mammary epithelial MCF-10A cells. MCF-10A cells transformed by either an activated human c-Ha-ras protooncogene (MCF-10A ras) or by overexpression of a nonactivated rat c-neu gene (MCF-10A neu) exhibited a 35% reduction in the response to AR in ADG when compared to MCF-10A cells, but AR was still as potent as EGF in these transformants. Exogenous AR exhibited only 15-20% of the activity of EGF in stimulating the anchorage-independent growth, a response that is normally dependent upon exogenous EGF, of the oncogene-transformed MCF-10A cells. MCF-10A cells express low levels of a 1.4-kb AR mRNA transcript, while MCF-10A ras and MCF-10A neu cells display a 15- to 30-fold increase in the levels of AR mRNA and endogenous AR protein as determined by Western blot analysis. Exogenous EGF was found to induced both the AR mRNA and protein in the MCF-10A parental and transformed cells. A 20-mer phosphorothioate antisense deoxyoligonucleotide complementary to the 5' sequence of AR mRNA was able to significantly reduce the levels of endogenous AR protein and to inhibit the EGF-stimulated ADG and anchorage-independent growth of MCF-10A ras and MCF-10A neu cells. These data suggest that AR may function as an EGF-dependent autocrine growth factor in mammary epithelial cells that have been transformed by either a point-mutated c-Ha-ras or c-neu.

Amphiregulin↗
PubMed1994

Substituted 2-benzothiazolamines as sodium flux inhibitors: quantitative structure-activity relationships and anticonvulsant activity.

Thirty-two aryl-substituted 2-benzothiazolamines have been tested for their ability to modulate sodium flux in rat cortical slices. A QSAR analysis, applied to these derivatives, showed a trend toward increasing potency as sodium flux inhibitors with increasing lipophilicity, decreasing size, and increasing electron withdrawal of the benzo ring substituents. Additionally, 4- or 5-substitution of the benzo ring was found to decrease potency. The combination of increased lipophilicity, small size, and electron withdrawal severely limited which groups were tolerated on the benzo ring, thus suggesting that the optimal substitution patterns have been prepared within this series. Nine of these compounds were potent inhibitors of veratridine-induced sodium flux (NaFl). These nine compounds also proved to be anticonvulsant in the maximal electroshock (MES) assay. Fourteen additional 2-benzothiazolamines demonstrated activity in the MES screen, yet exhibited no activity in the NaFl assay. These derivatives may be interacting at the sodium channel in a manner not discernible by the flux paradigm, or they may be acting by an alternative mechanism in vivo.

Animals↗
PubMed1994

A new 3D localization technique using quadratic field gradients.

A new method of 3D spatial selection using pulsed quadratic field gradients is presented. Like previous pulsed quadratic gradient methods the new method requires only two RF pulses to achieve selection in three dimensions. Unlike previous methods, however, precise alignment of linear and quadratic gradient coils is not required. This characteristic allows the method to be used with small or surface quadratic gradient coils. The method is demonstrated on phantom and rats.

Image Processing, Computer-Assisted↗
PubMed1994

Developmental effects of fumonisin B1-containing Fusarium moniliforme culture extract in CD1 mice.

Pregnant Charles River CD1 mice were treated with a semipurified extract of Fusarium moniliforme culture containing 0, 12.5, 25, 50 or 100 mg FB1/kg each day orally (diluted in distilled water) between gestational days (GD) 7 and 15 to evaluate the developmental toxicity of FB1. Following sacrifice of dams on GD 18, litters were examined for gross abnormalities and divided equally for skeletal or visceral examination by routine techniques. Significant maternal mortality was observed at doses of 50 and 100 mg FB1/kg. Dose-dependent decreases in maternal body weight gains, number of live offsprings per litter, and mean body weight of the offspring were produced at FB1 doses of 25 mg/kg or higher. The percentage of implants resorbed increased at all doses in a dose-dependant manner. A dose-dependant increase, except at the lowest dose tested, in the incidence of ossification deficits involving digits and sternum, short and wavy ribs, and hydrocephalus of lateral and third ventricles was also evident. Cleft palate was seen only at the highest FB1 dose. Maternal intoxication manifested as a dose-dependant increase in the severity of ascites associated mainly with increased histopathologic scores reflecting hepatocellular damage at day 18. Concommittant increases in serum alanine amino transferase (ALT) on GD 12, reflecting parenchymal liver cell damage, was also observed at all doses above 12.5 mg of FB1/kg. These results suggest that FB1-containing F. moniliforme culture extract is developmentally toxic in mice, and that this toxicity may be mediated by maternal hepatotoxicity.

Abnormalities, Drug-Induced↗
PubMed1994

Mechanism of initial attachment of cells derived from human bone to commonly used prosthetic materials during cell culture.

The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in cell culture. In this study the contribution that serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of cells cultured from explanted human bone (bone-derived cells) during the first 90 min of culture was determined for metallic and ceramic surfaces. The requirement for Fn or Vn for attachment and spreading of bone-derived cells onto stainless steel 316 (SS), titanium (Ti) and alumina (Al2O3) and to polyethyleneterephthalate (PET) was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of bone-derived cells onto SS, Ti and Al2O3 surfaces were reduced by 73-83% when the cells were seeded in medium containing serum from which the Vn had been removed. Cell attachment and spreading on these surfaces when seeded in medium containing Fn-depleted serum (which contained Vn) were not reduced to the same extent as in the medium containing Vn-depleted serum. The bone-derived cells failed to attach to the surfaces to the same extent when seeded in medium containing serum depleted of both Vn and Fn. Our results show that for human bone-derived cells, the attachment and spreading of cells onto SS, Ti and Al2O3 as well as PET during the first 90 min of a cell culture attachment assay are a function of adsorption of serum Vn onto the surface.

Aluminum Oxide↗
PubMed1994

Efficacy and safety of aerosolized ribavirin in young children hospitalized with influenza: a double-blind, multicenter, placebo-controlled trial.

We randomly assigned children hospitalized with influenza who had been ill < or = 48 hours and who had a temperature > or = 37.8 degrees C to receive either ribavirin or placebo. All patients had evaluations performed for fever reduction, use of acetaminophen for temperature > or = 38.3 degrees C, duration and severity of influenza symptoms, and feeding behavior. Sixty-two patients (35 in the placebo group, 27 in the ribavirin group) had a diagnosis of influenza confirmed by laboratory study. The groups did not differ significantly in age, initial signs and symptoms, or in distribution of influenza A or B infections. The time to reduction of temperature < or = 38.3 degrees C for the ribavirin group was 8.9 hours compared with 22.6 hours for the placebo group (p = 0.04). The mean duration of acetaminophen use was 7.4 hours in the ribavirin group and 16.3 hours in the placebo group (p = 0.14). There were no significant differences between the groups in outcome of respiratory rate, pulse rate, cough, or level of consciousness. Convalescent influenza antibody geometric mean titer for the placebo group was 9.8 compared with 3.6 for the ribavirin group (p = 0.04). Ribavirin was more effective than placebo in accelerating normalization of temperature but there were no other significant differences.

Acetaminophen↗
PubMed1994

Activation of adenosine A1 receptors in the nucleus accumbens impairs inhibitory avoidance memory.

Potent and highly selective adenosine A1 and A2 receptor agonists were bilaterally injected into the nucleus accumbens of mice 10 min prior to inhibitory avoidance training. Retention of the inhibitory avoidance response was assessed 24 h after training. Intra-ACB activation of A1 receptors, but not A2a receptor activation, significantly impaired the performance of mice during the subsequent retention test. Furthermore, the retention deficit produced by activation of A1 receptors was significantly attenuated by pretreating mice with a highly selective A1 receptor antagonist. These findings suggest that endogenous adenosine may modulate information processing in the ventral striatum via adenosine A1 receptors.

Adenosine↗
PubMed1994

HK-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney.

Studies assessing mechanisms of proximal tubular cell (PTC) physiology and pathophysiology increasingly utilize cell culture systems to avoid the complexity of whole organ/whole animal experiments. However, no well-differentiated PTC line derived from adult human kidney currently exists. Therefore, the goal of this research was to establish such a line by transduction with human papilloma virus (HPV 16) E6/E7 genes. A primary PTC culture from normal adult human renal cortex was exposed to a recombinant retrovirus containing the HPV 16 E6/E7 genes, resulting in a cell line designated HK-2 (human kidney-2) which has grown continuously in serum free media for more than one year. HK-2 cell growth is epidermal growth factor dependent and the cells retain a phenotype indicative of well-differentiated PTCs (positive for alkaline phosphatase, gamma glutamyltranspeptidase, leucine aminopeptidase, acid phosphatase, cytokeratin, alpha 3 beta 1 integrin, fibronectin; negative for factor VIII-related antigen, 6.19 antigen and CALLA endopeptidase). Furthermore, HK-2 cells retain functional characteristics of proximal tubular epithelium (Na+ dependent/phlorizin sensitive sugar transport; adenylate cyclase responsiveness to parathyroid, but not to antidiuretic, hormone). The E6/E7 genes are present in the HK-2 genome, as determined by PCR. To assess its potential usefulness as a tool for studying injury and repair, HK-2 cells were exposed to a toxic concentration of H2O2 +/- iron chelation (deferoxamine) or hydroxyl radical scavenger (Na benzoate) therapy. Only the former blocked H2O2 cytotoxicity, reproducing results previously obtained with freshly isolated rat proximal tubular segments. In conclusion, an immortalized adult human PTC line has been established by transduction with HPV 16 E6/E7 genes. It appears to be well-differentiated on the basis of its histochemical, immune cytochemical, and functional characteristics, and it can reproduce experimental results obtained with freshly isolated PTCs. Thus, this new PTC line could have substantial research application.

Adult↗
PubMed1994

Biphasic waveform defibrillation using a three-electrode transvenous lead system in humans.

INTRODUCTION: Biphasic waveform defibrillation is not always more efficacious than monophasic waveform defibrillation. METHODS AND RESULTS: Waveform efficacy appears to vary with the lead system used. In this prospective, randomized study, defibrillation efficacy with biphasic and monophasic single capacitor 120-microF, 65% tilt pulses was compared for a lead system consisting of right ventricular (RV), chest patch (CP), and superior vena cava (SVC) electrodes. Although this lead system is commonly used with monophasic pulses in transvenous defibrillators, few studies have examined the defibrillation efficacy of this lead system in man for biphasic waveform defibrillation. Fourteen cardiac arrest survivors undergoing defibrillator implantation were included in the study using pulses delivered from a cathodal RV electrode simultaneously to anodal SVC and CP electrodes. Biphasic and monophasic waveforms were recorded oscilloscopically to acquire defibrillation threshold (DFT) data on leading edge voltage requirements and for stored energy. The monophasic DFT voltage was 661 +/- 177 V compared to the biphasic DFT voltage of 451 +/- 185 V (P < 0.0001). The monophasic DFT stored energy was 28.0 +/- 13.4 J compared to the biphasic DFT stored energy of 14.1 +/- 12.4 J (P < 0.0001). The stored energy DFT was < or = 15 J in only 2 of 14 patients (15%) with monophasic defibrillation but < or = 15 J in 10 of 14 (71%) patients with biphasic defibrillation. CONCLUSION: These findings indicate that biphasic defibrillation with an RV, SVC, CP transvenous electrode system is substantially more efficient than monophasic defibrillation, allowing for higher numbers of patients to receive transvenous defibrillators with a relatively simple lead system at a satisfactory cutoff DFT safety margin of 15 J.

Adolescent↗