Transthoracically-induced high frequency ventilation.
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Animals↗
Biomedical subjects
H K Chang
Publications and source records attributed to H K Chang.
A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus.
The outer envelope of the 42-nm virion of the human hepatitis B virus (HBV) is composed of the large, the middle, and the major surface proteins. Whereas the middle and the major surface proteins are transcribed from the SPII promoter of the pre-S/S gene, the large surface protein is transcribed from the SPI promoter located upstream of SPII. We have previously shown that transcription of SPI (comprising nucleotides [nt] -380 to +17) occurs preferentially in differentiated hepatoma cell lines (H.K. Chang and L.P. Ting, Virology 170:176-183, 1989). In this report, we further demonstrated that a sequence of 95 base pairs in the upstream region of SPI (nt -95 to +17) was necessary and sufficient for such preferential expression in differentiated hepatoma cells. By analysis of the expression of the chloramphenicol acetyltransferase gene in a series of mutants with deletions at the 5' end of SPI, we identified a positive transcriptional cis-acting element mapping at nt -95 to -72 which appears to play a key role in the regulation of the expression of the large surface protein. This region shared a high degree of sequence homology with regulatory sequences of several liver-specific genes from human, mouse, and rat, with a consensus sequence (G/A)GTTA(A/C)TNNT(C/T)NNC(A/C). We further identified a nuclear factor present in the nuclear extracts of differentiated human hepatoma cell lines which interacted specifically with this element of the SPI promoter. This nuclear factor was similar to the rat liver-specific factor HNF-1, since an oligonucleotide containing the recognition sequence of HNF-1 could efficiently compete for the human factor in a footprinting assay. The sequence at nt -93 to -68 which was bound by this factor in SPI was termed the HNF-1-binding element. Activation of the SPI promoter by human differentiated hepatocyte nuclear factor 1, described in this report, probably explains, first, the formation of the 42-nm virion specifically in liver but not in several other tissues despite the synthesis of the middle and the major surface proteins in those tissues, and second, why only differentiated hepatoma cell lines are able to produce 42-nm-like virion particles on transfection by HBV DNA.
Base Sequence↗
Transverse images of the human thoracic trachea during forced expiration.
The thoracic trachea and the proximal portion of the major bronchi were imaged in five normal volunteers during a forced expiration maneuver using a cine-computer-tomography system. Sixteen images of two contiguous slices were obtained in less than 1 is while expiratory flow was recorded at the mouth. The area of the thoracic trachea decreased rapidly as flow rate rose to its maximum and the wave of collapse propagated distally. The compressive narrowing of both the pars membranacea and the ventrolateral wall was asymmetric. A contact area appeared between the posterior and the left lateral walls. In one subject the trachea was imaged during the entire maneuver with a lower scan frequency. By 725 ms after the beginning of the forced expiration, the area had first decreased to 15% of its initial value and then reincreased to 46% of its initial value. It stayed constant for the remainder of the maneuver. The measured maximum air velocity was greater than the estimated local wave velocity.
Adult↗
Effects of high-frequency chest wall oscillation on respiratory control in humans.
We studied the spontaneous breathing patterns of 10 normal adult volunteers during high-frequency chest wall oscillation (HFCWO), accomplished by inflating and deflating a vest worn around each subject's thorax at 2.5 Hz. Tidal volumes generated by HFCWO averaged 100 ml. Mean vest pressure was maintained at approximately 35 cm H2O throughout each experiment, even when HFCWO was not applied. During HFCWO, subjects were instructed occasionally to exhale deeply to obtain end-tidal samples representative of PACO2. HFCWO increased the breath-to-breath variability of spontaneous respiration in all subjects, prolonging expiratory pauses and producing short apneas in some cases. PACO2 decreased significantly (p less than 0.05). The effects on minute ventilation, tidal volume, and inspiratory and expiratory durations remained variable across subjects, even when differences in PACO2 between control and HFCWO states were reduced through inhalation of a low CO2 mixture. None of the changes were statistically significant, although average expiratory duration increased by 29%. Ventilatory responses to CO2 with and without HFCWO were also measured. Normocapnic (PACO2 = 40 mm Hg) ventilatory drive increased significantly (p less than 0.05) in six subjects (Type 1 response) and decreased substantially in the others (Type 2 response); with hypercapnia, the changes in drive were attenuated in both groups. Consequently, CO2 sensitivity decreased in Type 1 subjects and increased in Type 2 subjects. A simple analysis based on this result shows that with HFCWO, Type 2 subjects breathing air will tend to have a lower spontaneous minute ventilation and become hypercapnic. Type 1 subjects will become hypocapnic, but minute ventilation may be higher or lower than control.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Evaluation of lung mechanics in rabbits using short duration flow pulses.
An alternative method of evaluating pulmonary mechanical function that uses short duration flow pulses was applied in five adult rabbits with high frequency flow interruption (HFFI) at 4 cycles per second. Variations in the total pressure across the respiratory system were partitioned into separate lungs and chest wall components, and the mechanical impedance of each component was evaluated in the range of 4 to 40 Hz using cross and power spectral analysis and spectral averaging. The resistances, R, of the respiratory system, lungs, and chest wall were 23.5 (2.3 SD), 18.6 (2.8), and 4.9 (1.5) cm H2O.L-1.s, respectively. These values were similar to R obtained by the conventional method at ordinary rates of ventilation, with the exception of chest wall resistance, which was approximately 50% smaller than R obtained by the conventional method. The compliances of the respiratory system, lungs and chest wall were 1.40 (0.19), 2.88 (0.94), and 2.85 (0.86) ml.cm H2O-1, respectively. In all cases, compliance values obtained by pulse analysis were roughly 70% of the values obtained by the conventional method. The smaller compliance values obtained with the pulse method may reflect the multicompartment behavior of the lungs and chest wall at the high frequencies found in the pulse spectra. We conclude that the response of the respiratory system to short duration flow pulses may be used to evaluate pulmonary mechanical function. The brief duration of the flow pulse suggests that this method may be well suited to evaluate lung function in uncooperative subjects, particularly newborns and premature infants.
Airway Resistance↗
Estimation of pulmonary capillary pressure in intact dog lungs using the arterial occlusion technique.
We describe a technique for the estimation of pulmonary capillary pressure from arterial pressure profiles recorded during occlusion of blood flow in a quasi-intact dog lung preparation. In this preparation, the lower lobe of the left lung was perfused directly by the right ventricle while its venous outflow was collected in a reservoir before being recirculated into the animal. Arterial occlusion maneuvers were accomplished by inflating the balloon of a Swan-Ganz catheter positioned in the left lower lobe artery. The instant of occlusion was precisely determined as the time during the balloon inflation when the pressure inside the balloon reached a maximal value. The arterial pressure profile recorded after inflation of the Swan-Ganz balloon was analyzed in the following manner to estimate the capillary pressure: first, a single exponential approximation of the pressure decay was computed over a short segment of the postocclusion pressure data. The extrapolation of the exponential fit toward the instant of occlusion (Pa0) yielded a first estimate of the capillary pressure. A second estimate was selected as point at which the pressure tracing merged with the exponential fit (Pa0+). These estimates were compared to the double occlusion pressure, which was used as a reference value of the capillary pressure (Pcap). Our results show that the extrapolation of the exponential fit toward the instant of occlusion gave an accurate estimation of the pulmonary capillary pressure over a wide range of pressures: Pa0 = 0.95 (+/- 0.04).Pcap, and the slope of this relationship was not statistically different from 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Adenomatous polyps of the prostatic urethra. A report of four cases].
A benign prostatic urethral polyp is considered as an unusual lesion of the urethra. It attracts the patient or doctor's attention only when hematuria or hemospermia is noted. From August 1987 to June 1988, the authors found four cases of posterior urethral polyps in the Taitung Branch of Mackay Memorial Hospital. Hematuria was found in all of the 4 patients and hemospermia was found in one. Three patients presented gross hematuria, and one microscopic hematuria. Of the four, two had suprapubic soreness; one had perineal discomfort; and only one manifested no symptoms at all. All of the patients underwent a cystoscopic biopsy, and their specimens were stained and studied by the immunoperoxidase method. All of the specimens were PSA positive, and presented a picture of adenomatous polyp. Only one patient received transurethral electrocoagulation because of continued hematuria and perineal discomfort that persisted even after a two week medical course that appeared to be more effective to the previous one. In conclusion, the authors believe that more of such lesions will be discovered when more attention is paid to the posterior urethra; when adenomatous polyps are suspected in patients who have the above symptoms; and when polyps are considered as a possibility in the differential diagnosis.
Adult↗
Convection, diffusion and their interaction in the bronchial tree.
The bronchial tree is an asymmetric multi-generation conduit for air to pass through. Breathing is a time-varying, cyclic process. Therefore, gas transport in the bronchial tree during breathing is a problem with both spatial and temporal complexities. However, it is possible to gain a fair understanding of this complex process by examining the roles of bulk convection, molecular diffusion and the various modes of their interaction. Convection brings the inspired gas into the peripheral region of the lung and removes the mixed inspired-resident gas from the lung. During the post-inspiratory and post-expiratory pauses and in the very distal regions of the lung, molecular diffusion alone is responsible for the mixing process. Convection and diffusion together are responsible for establishing a quasi-steady front of the inspired gas in the peripheral lung region. The position of the front depends on lung volume, tidal volume, inspiratory flow-rate as well as diffusivity of the inspired gas. Taylor-type dispersion, while certainly existing in the lung, and despite its gas mixing potentials, is of questionable effectiveness in the overall gas transport process in the bronchial tree. The various modes of interaction between convection and diffusion are likely to improve gas mixing in the bronchial tree and have an effect on the phase II of the single-breath washout curve.
Animals↗
A nonlinear model of respiratory mechanics in emphysematous lungs.
Existing mechanical models of chronic obstructive lung disease have failed to explain a number of experimental findings of airway obstruction, e.g., the varying manners of frequency dependence of resistance (FDR). Departing from the parallel-unit concept and attempting to account for the "check-valve" mechanism in the emphysematous lung, we proposed a single-compartment lung model with a nonlinear pressure-flow relationship: P + P* = LV + K1V + K3(V +/- V*)3 + V/c, where P* = K3V*, V* is a constant. The plus and minus signs in the cubic term indicate the expiratory and inspiratory check valves, respectively. The choice of an asymmetric P - V relation reflects several properties of emphysematous lungs such as airflow limitation and higher expiratory resistance. Implementation of the above equation using sine wave, white noise, and step inputs resulted in various forms of FDR at frequencies between 0 and 40 Hz depending on the type of input used. Resistance was most sensitive to changes in input pressure amplitude. The model's results suggest that the P - V nonlinearity can have a significant influence on the impedance construct in obstructed lung disease.
Airway Resistance↗
Lung hyperinflation in isolated dog lungs during high-frequency oscillation.
To study the phenomenon of lung hyperinflation (LHI), i.e., an increase in lung volume without a concomitant rise in airway pressure, we measured lung volume changes in isolated dog lungs during high-frequency oscillation (HFO) with air, He, and SF6 and with mean tracheal pressure controlled at 2.5, 5.0, and 7.5 cmH2O. The tidal volume and frequency used were 1.5 ml/kg body wt and 20 Hz, respectively. LHI was observed during HFO in all cases except for a few trials with He. The degree of LHI was inversely related to mean tracheal pressure and varied directly with gas density. Maximum expiratory flow rate (Vmax) was measured during forced expiration induced by a vacuum source (-150 cmH2O) at the trachea. Vmax was consistently higher than the peak oscillatory flow rate (Vosc) during HFO, demonstrating that overall expiratory flow limitation did not cause LHI in isolated dog lungs. Asymmetry of inspiratory and expiratory impedances seems to be one cause of LHI, although other factors are involved.
Airway Resistance↗
Mucus transport by high-frequency nonsymmetrical oscillatory airflow.
To study air-mucus interaction as a possible mechanism of tracheal mucus transport and to test the validity of using surface tracer displacement to indicate bulk mucus transport, we performed a combined experimental-theoretical study. We hypothesized that the mucus mass is moved by the difference between expiratory and inspiratory velocities. The rate of transport of a layer of simulated mucus lining the bottom of a rectangular trough was measured in two ways during oscillatory air flow. Peak velocity ratios (R) from 1.0 to 2.0, frequencies (f) between 7 and 13 Hz, and tidal volumes (VT) between 50 and 100 ml were generated by a custom-made pump. The experimental results demonstrate that measuring the displacement of a tracer deposited on the surface of the mucus layer is equivalent to measuring bulk mucus movement by weight. Moreover the measured mucus velocities (micron) correlate well with a theoretical model which predicts that micron is proportional to delta VT f1.5 (R-1). These results suggest that shearing at the air-mucus interface could be a significant factor in the enhanced tracheal mucus clearance during high-frequency chest wall oscillation.
Animals↗
Interpretation of the krypton-81m dynamic series: the distribution of a tidal breath.
Lung scans during cyclic breathing of krypton-81m, an isotope with a 13-s half-life, were acquired in "list mode," where both temporal and spatial information are preserved. Subjects in the left lateral decubitus position breathed with two tidal volumes at each of two frequencies. Profiles of total activity over the acquisition period were examined. They showed little effect of frequency or tidal volume on the distribution of air between dependent and non-dependent regions. Dynamic series for ensemble-averaged breaths were constructed. The regional flow per unit volume was shown to correspond to the time derivative of the regional activity of the dynamic series divided by the corresponding activity. Both the relative timing of the gas flow to different lung regions and the flow per unit volume as a function of time were obtained from the dynamic series. The dependent lung was seen to be better ventilated throughout the respiratory cycle except for brief periods at the start of inspiration and the end of expiration. Most of the dead-space gas can be construed to enter and leave the dependent lung.
Female↗
Airflow and normal lung sounds.
The relationship between total air flow and normal breath sounds recorded at 2 sites on the chest was investigated. Sounds were measured during rhythmic breathing, during flow rate tracking, and during flow rate tracking against an external resistance by subjects seated and in the left lateral decubitus position. The sound amplitude during inspiration varied directly with the square of the air flow at the mouth. Changes in subject position and breathing pattern altered the gain between the square of the flow and the sound amplitude but not the functional relationship.
Adult↗
Gas exchange during high frequency flow-interruption in rabbits before and after bronchoalveolar lavage.
The performance of a high frequency flow-interrupter (HFFI) type neonatal ventilator was evaluated on nine adult rabbits (control) and on five adult rabbits after bronchoalveolar lavage (BAL). Tidal volumes and airway pressures were measured during conventional ventilation and during HFFI at rates of 4, 6, 8, 10, and 12 cycles/s. Tidal volumes were adjusted to maintain PaCO2 between 35 and 42 mm Hg in control rabbits and 35-55 mm Hg in BAL rabbits; a positive end-expiratory pressure of 4 cm H2O was applied to BAL rabbits to reduce atelectasis and improve gas exchange. The normalized tidal volume required to maintain PaCO2 within the specified range during HFFI varied between 2.02 ml/kg (0.30 SD) and 2.55 (0.41) in control rabbits and between 2.65 (0.57) and 2.97 (0.51) in BAL rabbits. In neither group did the normalized tidal volume vary systematically with the rate of ventilation (p less than 0.05). Mean airway pressures were lower during HFFI than during conventional ventilation in control rabbits but comparable in the BAL group. Peak inflation pressures were greater during HFFI than conventional ventilation in control rabbits but similar in the BAL group. End-expiratory lung volume was not affected by ventilation rate during HFFI in control rabbits. We conclude 1) that HFFI can maintain gas exchange in rabbits suffering from acute respiratory distress with airway pressures that are comparable to those measured during conventional ventilation and 2) the capacity of HFFI to ventilate the lungs with significantly lower airway pressures than conventional ventilation depends, in part, on the condition of the lungs.
Animals↗
Expression of oncogenes in human hepatoma cell lines.
The expression of 20 known cellular proto-oncogenes in human well-differentiated hepatoma cell line Hep3B and poorly-differentiated hepatoma cell line HA22T/VGH was studied by Northern blot hybridization. Among the cellular proto-oncogenes examined, both cell lines express protein kinase genes including fps, mos and raf; PDGF B chain sis gene; GTP/GDP binding protein gene Ha-ras and nuclear protein genes including fos and myc. The expression of yes, abl, ros, src, erb-B, erb-A, fms, Ki-ras, myb, rel and bas genes was not detected in both cell lines.
Blotting, Northern↗
The enhancer sequence of human hepatitis B virus can enhance the activity of its surface gene promoter.
The transcriptional enhancer sequence has recently been demonstrated in the hepatitis B viral genome. This enhancer sequence has also been shown to increase the activity of HBcAg gene promoter. Using the chloramphenicol acetyltransferase gene expression system, we demonstrated that the intrinsic promoter activity of HBsAg gene promoter was stronger than that of HBcAg gene promoter in both human hepatoma cell lines, Hep3B and HuH-7. Furthermore, we showed that the HBV enhancer sequence not only stimulated the HBcAg gene promoter activity, but also stimulated the HBsAg gene promoter activity in both Hep3B and HuH-7 cells. The enhancer sequence increased the HBsAg gene promoter activity 20-fold in both Hep3B and HuH-7 cell lines, while the increase of the HBcAg gene promoter was 2- and 8-fold in Hep3B and HuH-7 cells, respectively.
Acetyltransferases↗
Effects of lung volume and alveolar surface tension on pulmonary vascular resistance.
Utilizing the arterial and venous occlusion technique, the effects of lung inflation and deflation on the resistance of alveolar and extraalveolar vessels were measured in the dog in an isolated left lower lobe preparation. The lobe was inflated and deflated slowly (45 s) at constant speed. Two volumes at equal alveolar pressure (Palv = 9.9 +/- 0.6 mmHg) and two pressures (13.8 +/- 0.8 mmHg, inflation; 4.8 +/- 0.5 mmHg, deflation) at equal volumes during inflation and deflation were studied. The total vascular pressure drop was divided into three segments: arterial (delta Pa), middle (delta Pm), and venous (delta Pv). During inflation and deflation the changes in pulmonary arterial pressure were primarily due to changes in the resistance of the alveolar vessels. At equal Palv (9.9 mmHg), delta Pm was 10.3 +/- 1.2 mmHg during deflation compared with 6.8 +/- 1.1 mmHg during inflation. At equal lung volume, delta Pm was 10.2 +/- 1.5 mmHg during inflation (Palv = 13.8 mmHg) and 5.0 +/- 0.7 mmHg during deflation (Palv = 4.8 mmHg). These measurements suggest that the alveolar pressure was transmitted more effectively to the alveolar vessels during deflation due to a lower alveolar surface tension. It was estimated that at midlung volume, the perimicrovascular pressure was 3.5-3.8 mmHg greater during deflation than during inflation.
Animals↗
Measurement of pleural pressure at low and high frequencies in normal rabbits.
In eight tracheotomized adult rabbits placed in the supine position, we employed a catheter-tip piezoresistive pressure transducer to measure esophageal pressure (Pes) and assessed the validity of taking the changes in Pes to be the changes in pleural pressure (Ppl). We applied an occlusion test in which the tracheal cannula was occluded during either spontaneous inspiratory efforts or body surface oscillations ranging from 3 to 50 Hz. The relationship between Pes and airway opening pressure (Pao) was recorded. In all instances, the changes in Pes and Pao were virtually identical in both amplitude and phase. We conclude that, as evaluated by the occlusion test, a catheter-tip pressure transducer placed in the esophagus of rabbits can give adequate estimation of local pleural changes up to at least 50 Hz.
Animals↗