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Biomedical subjects

R Low

Publications and source records attributed to R Low.

At least 19 recordsLinked to original sources

Down-regulation of plant V-type H+ -ATPase genes after light-induced inhibition of growth.

Cell extension growth in the mesocotyl tip of dark-grown Zea mays L. seedlings is dependent on vacuole enlargement and massive flux of ER and Golgi vesicles. Water flow into the expanding vacuole is driven by ion accumulation, which in turn is energized by the vacuolar H+-ATPase (V-ATPase). The V-ATPase energizes the secondary ion transport into the expanding vacuole. As light exposure leads to a strong inhibition of extension growth, the effect of light on transcript levels for subunits A and c of the V-ATPase was analyzed. Partial homologous cDNAs for subunit A and two isoforms of subunit c were cloned by RT-PCR. In dark-grown seedlings transcript levels for both subunits were much higher in the growing mesocotyl tip than in the fully differentiated mesocotyl tissue. Only in the tip region did light exposure lead to a strong and coordinate down-regulation of both mRNAs whereas in the differentiated mesocotyl only a slight decrease was observed. The results indicate that expression of the 'housekeeping' V-type H+-ATPase is strongly regulated in response to growth rate.

Adenosine Triphosphatases

Does a sodium-free buffer affect QRS width in experimental amitriptyline overdose?

STUDY OBJECTIVES: We carried out this study to determine the effects of pH alteration on QRS width with administration of tromethamine, a non-sodium-containing buffering agent, in experimental amitriptyline overdose. DESIGN: Prospective, nonblinded trial. PARTICIPANTS: Adult mongrel dogs. INTERVENTIONS: Pentobarbital-anesthetized dogs were overdosed with amitriptyline 5 mg/kg followed by infusion at 1.0 mg/kg/minute until the QRS width doubled, then decreased to .5 mg/kg/minute until the end of the experiment. At two defined points of toxicity, the dose of tromethamine required to raise the pH to 7.50 +/- 4 was given. pH and QRS width at a speed of 100 mm/second were measured over a 30-minute period after each tromethamine dose. Data were analyzed with non-linear-regression analysis. RESULTS: At toxicity 1 the mean pH was 7.32, with a QRS width of 11.6 mm. Two minutes after the tromethamine dose the pH rose to 7.51, with narrowing of the QRS width to 8.4 mm. At toxicity 2 the pH was 7.40, with QRS width of 10.6 mm. Two minutes after tromethamine, the pH rose to 7.49 and the QRS width decreased to 9.7 mm. Regression analysis showed a correlation between pH and QRS width; as pH increased, QRS width decreased (P = .0001). CONCLUSION: Cardiac toxicity of amitriptyline overdose, as manifested by QRS widening, is reversible by pH changes alone.

Amitriptyline

The 1-month outcome of patients with a low probability Technegas ventilation/perfusion lung scan.

The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.

Female

Characterization of vascular smooth muscle cell phenotype in long-term culture.

Studies of bovine carotid artery smooth muscle cells, during long-term in vitro subcultivation (up to 100 population doublings), have revealed phenotypic heterogeneity among cells, as characterized by differences in proliferative behavior, cell morphology, and contractile-cytoskeletal protein profiles. In vivo, smooth muscle cells were spindle-shaped and expressed desmin and alpha-smooth muscle actin (50% of total actin) as their predominant cytoskeletal and contractile proteins. Within 24 h of culture, vimentin rather than desmin was the predominant intermediate filament protein, with little change in alpha-actin content. Upon initial subcultivation, all cells were flattened and fibroblastic in appearance with a concomitant fivefold reduction in alpha-actin content, whereas the beta and gamma nonmuscle actins predominated. In three out of four cell lines studied, fluctuations in proliferative activity were observed during the life span of the culture. These spontaneous fluctuations in proliferation were accompanied by coordinated changes in morphology and contractile-cytoskeletal protein profiles. During periods of enhanced proliferation a significant proportion of cells reverted to their original spindle-shaped morphology with a simultaneous increase in alpha-actin content (20 to 30% of total actin). These results suggest that in long-term culture smooth muscle cells undergo spontaneous modulations in cell phenotype and may serve as a useful model for studying the regulation of intracellular protein expression.

Actins

Alpha-smooth muscle actin in parenchymal cells of bleomycin-injured rat lung.

Bleomycin causes focally diffuse interstitial fibrosis characterized by increases in the number and volume of contractile filament-laden parenchymal cells, as well as increased parenchymal contractility. However, the origin of these cells and their relationship to altered contractility, remain unknown. We now have used immunohistochemical methods to ask if cells containing smooth muscle actin and myosin are present in involved regions of parenchyma. Staining of the parenchyma of control lungs with a monoclonal antibody against alpha-smooth muscle actin is sparse, consisting of reactivity with the alveolar entrance ring (septal tip) cells as well as occasional reactivity of alveolar wall cells that may represent pericytes or contractile interstitial cells. Increased alpha-smooth muscle actin staining was observed in areas of parenchymal damage in lungs from animals sacrificed between 1 and 4 weeks postbleomycin instillation. This reactivity included altered staining of the airway and vessel smooth muscle coat as well as thickened septal tips. In addition, newly reactive cells were observed in interstitial and intraalveolar regions and in bands of thickened submesothelial tissue. Staining was most intense in the focal fibrotic lesions which are characteristic of this injury. By contrast, parenchymal reactivity with a polyclonal antibody against smooth muscle myosin at the later time points shows only a mild increase in punctate staining in the damaged foci. We hypothesize that the substantial increase in alpha-smooth muscle actin containing cells in fibrotic regions of involved parenchyma after bleomycin injury is responsible for the altered morphologic, biochemical, and mechanical properties that we have observed.

Actins

Advance prediction of transthoracic impedance in human defibrillation and cardioversion: importance of impedance in determining the success of low-energy shocks.

The purposes of this study were to evaluate a method that predicts transthoracic impedance in advance of defibrillating shocks in humans and to assess the importance of transthoracic impedance in low-energy defibrillation. Via defibrillator electrodes we applied 31 kHz current to the chest during the defibrillator charge cycle, before the defibrillating shock was actually delivered. The current flow was limited by transthoracic impedance; a microprocessor monitored the predischarge current flow and determined the predischarge impedance by calibration against known resistance values. Actual impedance to the defibrillating shock was also determined and compared with the predicted impedance. With this approach we predicted impedance in 19 patients who received 66 shocks for ventricular and atrial arrhythmias. Predicted impedance (y) correlated very well with actual impedance (x):y = .90x + 11.3; r = .97. To determine the importance of impedance in defibrillation and cardioversion, we prospectively gathered data from 96 patients who received shocks of various energies for ventricular or atrial arrhythmias. In patients with high transthoracic impedance (greater than 97 omega), low-energy shocks (less than or equal to 100 J) for ventricular defibrillation had only a 20% success rate as opposed to a 70% success rate for low-energy shocks in patients with low or average impedance (p less than .05). We conclude that transthoracic impedance can be accurately predicted in advance of defibrillation and cardioversion. This method permits the preshock identification of patients with high impedance in whom attempts to defibrillate with low-energy shocks are inappropriate.

Arrhythmias, Cardiac

Mast cell heterogeneity and hyperplasia in bleomycin-induced pulmonary fibrosis of rats.

The distribution, density, and histochemical subtype of mast cells were studied in the respiratory tract of rats with bleomycin-induced pulmonary fibrosis. In normal rats, mast cell densities were highest in the trachea and lowest in the bronchus and parenchyma. Two histochemically distinct mast cell populations were identified in the mucosa adjacent to the tracheal cartilage, but elsewhere only a single population of typical connective tissuelike mast cells was found. After intratracheally administered bleomycin, lung histamine levels (micrograms/g wet weight) increased as much as 14-fold by Day 50. Pulmonary mast cell changes were present early in the fibrotic process, and by Day 14 the mast cell density in the parenchyma was 10 times normal. These parenchymal mast cells were histochemically of the connective tissue type. Thus, pronounced mast cell hyperplasia occurs during the evolution of experimental pulmonary fibrosis. This model provides a powerful tool to study pulmonary mast cells and to identify their role in fibrotic disease.

Animals

Circadian rhythm of hourly ventricular arrhythmia frequency in man.

Three twenty-four hour electrocardiographic recordings from 164 untreated patients were analyzed. A clear, statistically significant, diurnal pattern in hourly ventricular arrhythmia frequency was found. It was consistent across days and between seven diagnostic groups. A high frequency Noon to 4:00 PM peak contrasted with a low frequency 1:00 AM to 5:00 AM trough with zero hourly frequencies not uncommonly present. These findings appear applicable to large ambulatory populations and may well influence the design of future investigations of modalities which alter ventricular arrhythmia frequency.

Aged

Auditory evoked potentials compared to performance measures and EEG in assessing excessive daytime sleepiness in narcolepsy-cataplexy.

The AEP to the repetitive stimuli of the Wilkinson auditory vigilance task was compared between untreated patients with narcolepsy-cataplexy and matched controls for periods during which the tones were preceded by 13 sec or more of wakefulness (defined by EEG-polygraphic criteria). During these periods it had been found previously that narcoleptics did not perform worse than did controls. The AEP, nevertheless, showed significant differences for narcoleptics. These were similar to changes described for drowsiness in normals. The AEP, therefore, showed changes related to excessive day time drowsines in narcolepsy-cataplexy when a sensitive performane measure and visual analysis of EEG-polygraphic recordings did not.

Adult

Thermodynamics of mixing of dipalmitoyl phosphatidylcholine and egg phosphatidylcholine in hydrated bilayers.

Dipalmitoyl phosphatidylcholine (DPPC) and egg phosphatidylcholine (egg PC) are not completely miscible at all temperatures. Their phase diagram was determined by differential scanning calorimetry (DSC) of aqueous mixtures of the two. From the integrated DSX curves we obtained the enthalpy of solution of DPPC in egg PC delta hs, as a function of the mole fraction of DPPC, X, and using the empirical relationship between delta hs and X, the solubility Xsat as a function of temperature, T. The latter could be described by the semiempirical relationship: R1nXsat = a + blnT - c/T, where a = 6.57 X 10(-2) kcal.mol-1. degree -1 and c = 20.5 kcal. mol-1 (1 cal = 4.1868 J); the coefficient b was very small and could be ignored. The quantity delta hs can be given as XdeltahDPPC + deltah mix, where deltah DPPC is the gel - liquid crystalline transition enthalpy of DPPC (8.74 kcal.mol-1) and deltah mix is the enthalpy of mixing the two liquid crystalline lipids. Deltahmix depends on X in approximately a parabolic fashion, having a maximal value of 4.8 kcal.mol-1 at X = 0.6. It was shown that both the solubility and mixing enthalpy data can be described by the theory of regular solutions (RST). In RST, the activity coefficient of the solute (component 2) of a binary solution is given by RTIngamma 2 = (1 - Theta2)2deltaU, while the mixing enthalpy is given by delta hmix = Theta1 Theta2 delta U/v2, where Theta1 and Theta2 are the volume fractions of solvent and solute (egg PC and DPPC, respectively), v2 is the partial molar volume of DPPC, and deltaU is the energy change per mole on interchanging a DPPC and an egg PC molecule between their respective liquid crystalline phases. The thermodynamic data are accurately described by RST, the molar volume of DPPC being found to be about half that of egg PC solution and the interchange energy deltaU having a value of 10-11 kcal.mol-1. There was some evidence that deltaU may be an increasing function of temperature. The large value of the deltaU accounts for the pronounced temperature dependence of the solubility Xsat, which decreases from 0.35 at 35 degrees C to 0.02 at 10 degrees C. The presence of cholesterol in the mixtures decreases both the transition enthalpy of DPPC and the mixing enthalpy in a linear fashion, so that deltahs is zero at Xcholesterol greater than or equal to 0.2. The results are consistent with recent data including the formation of a PC-cholesterol complex oc stoichiometry approximately 4:1.

Animals

Efficacy of percutaneous transluminal coronary recanalization utilizing streptokinase thrombolysis in patients with acute myocardial infarction.

Since coronary thrombosis is a principal factor in the evolving necrotic process in the majority of patients with acute myocardial infarction (AMI), a prospective study was conducted in 25 AMI patients who underwent expeditious coronary arteriography. Of these patients, 22 with totally occluding thrombus also received early streptokinase (STK) administration. STK was given by intracoronary (20 patients) or systemic (two patients) infusion, 2000 to 50,000 IU/min, to a total dose of 125,000 to 500,000 IU within 10 hours of AMI symptom onset. Eighteen patients had angiographically visualized successful coronary thrombolysis; the shorter the interval between onset of symptoms to treatment, the more rapid was the clot dissolution. Successful thrombolysis occurred concomitantly with readily managed reperfusion ventricular tachyarrhythmias in nearly all patients. In addition, STK recanalization resulted in relief of ongoing chest pain in 10 of 12 patients, 10 of 16 evidenced immediate normalization of hyperacute ST segment abnormalities, and 8 of 14 demonstrated subsequent improvement of angiographically visualized left ventricular (LV) ejection fraction. In the percutaneous transluminal coronary recanalization (PTCR) procedure, the step of using a soft-tipped guide wire itself was transiently useful in only one of seven patients in whom this was attempted; reocclusion took place without added STK therapy. Nitroglycerin (NTG) alone produced only slight distal patency in but 1 of 19 patients with coronary occlusion given the nitrate. Importantly, in 14 control AMI patients receiving conventional treatment without STK, 10 showed angiographically complete occlusion of the coronary artery supplying the infarct region 1 month after infarction, thereby excluding spontaneous clot lysis mimicking STK-PTCR-induced reperfusion. These data support the concept that coronary occlusion by thrombosis is inherently involved with AMI and that rapid PTCR application of intracoronary STK provides potent thrombolysis, superior to that provided by NTG and guide wire passage in reestablishing coronary flow with attendant salvage of jeopardized myocardium and with subsequently improved LV function.

Adult