[Correlation between chest CT features and clinical characteristics of patients with bronchiectasis].

Objective: To analyze the features of chest CT imaging in adult patients with bronchiectasis and explore its correlation with clinical characteristics. Methods: From January 2010 to December 2017, patients with bronchiectasis diagnosed by chest high-resolution CT (HRCT) and aged at or above 18 years old in 5 general hospitals of Shandong province were included in the study. The correlations between the HRCT imaging features and etiology, clinical manifestations, lung function, sputum culture, prognosis and other characteristics were analyzed. Results: There were 410 bronchiectasis patients included in the study. The chest HRCT imaging of bronchiectasis were divided into three types, including columnar 46.8%, cystic 45.9% and varicose 7.3%, respectively. The HRCT imaging score was [6.0 (4.0, 7.0)]. In addition, the most common etiology of bronchiectasis was idiopathic (262, 69.3%). The proportion of idiopathic bronchiectasis in cystic bronchiectasis patients was significantly higher than that in columnar and varicose bronchiectasis (71.8% vs 58.3%, 50.0%; both P<0.017). Compared with columnar bronchiectasis, patients with cystic bronchiectasis were more likely to suffer from clinical manifestations such as cough, dyspnea, fever and wet rales (P<0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 were more likely to suffer from cough, dyspnea, fever, wet rales and clubbing (P<0.017). The proportions of pulmonary ventilatory dysfunction were significantly greater in patients with cystic bronchiectasis and varicose bronchiectasis than columnar bronchiectasis (86.7%, 86.7% vs 51.0%; both P<0.017). The HRCT scores were significantly negatively correlated with pulmonary function (P<0.001). The number of acute exacerbations, hospitalizations, and bronchiectasis severe index scores in patients with cystic bronchiectasis were significantly higher than those with columnar bronchiectasis (P<0.017). There was a significantly positive correlation between HRCT scores and the number of acute exacerbations, hospitalizations and the bronchiectasis severity index scores (P<0.001). The mortality of patients with cystic and varicose bronchiectasis was significantly higher than that of patients with columnar bronchiectasis (9.0%, 10.0% vs 2.1%; both P<0.017). Compared with patients with HRCT scores of 1 to 4, patients with scores ≥8 had a higher mortality rate (15.9% vs 0.9%; P<0.017). Conclusions: There is a correlation between HRCT findings and clinical manifestations in patients with bronchiectasis. The clinical manifestations, lung function and prognosis of patients with cystic bronchiectasis are worse than those of the columnar bronchiectasis; the higher the HRCT scores are, the worse the clinical manifestations, lung function and prognosis of the patients are.

Increased risk of a herpes zoster attack in patients receiving androgen deprivation therapy for prostate cancer.

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population-based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3-year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person-years was 1.80 (95% CI: 1.41-2.25) during the 3-year follow-up period. In particular, incidence rates of HZ per 100 person-years were 2.36 (95% CI: 1.75-3.13) and 1.24 (95% CI: 0.81-1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3-year follow-up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13-3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ.

Responses of inferior colliculus neurons to sounds presented at different rates in anesthetized albino mouse.

We recorded extracellular activity from 402 single units located in the inferior colliculus (IC) of barbiturate-anesthetized albino mice. The stimuli were pure tones at characteristic frequency (CF) with durations of 10, 40 and 100 ms and intensities ranged from 5 to 25 dB above unit's minimum threshold (MT). The tones were presented with different repetition rates (RRs) ranging from 0.2 to 20.0 Hz. At low intensities (5 dB above MT, determined at RR of 0.5 Hz) the great majority of units exhibited a strong decline of their responses when the stimulus RR was increased. About one-half of the units did not respond to 40 ms tones when they were stimulated with the RR of 3.0 Hz. This effect was even more pronounced for 100 ms tones. Generally, the increase in stimulus intensity led to an increase in the high-frequency border of RR. Nevertheless, even at intensities of 20-30 dB above MT, some units showed no response when the RR exceeded 5.0 Hz. In many cases the band-pass or high-pass duration tuning of the single unit was transformed to low-pass or all-pass when the rate was low enough to guarantee the independence of successive presentations of the stimuli. Responses of a very small group of IC units, however, were enhanced when the RR was increased. Our data have shown that the changes in the RR radically modify many features of the neural response (number of spikes, latency, discharge pattern, duration selectivity). We suggest that long-lasting inhibitory processes may be induced by low intensity stimuli in many units of the IC.

Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver.

A bioartificial liver (BAL) employing xenogeneic hepatocytes has been developed as a potential interim support for patients in hepatic failure. For application in human therapy, the BAL requires a substantial increase in liver-specific functions. Cultivation of hepatocytes as spheroids leads to enhanced liver specific functions. We explored the possibility of entrapping spheroids into the BAL in order to improve device performance. Rat hepatocyte spheroids were entrapped in collagen gel within the lumen fibers of the BAL. The morphology and ultrastructure of collagen-entrapped spheroids resembled those of suspended spheroids formed on petri dishes. Albumin synthesis and P-450 enzyme activity were measured as markers of liver specific functions of spheroids entrapped in the BAL. At least a 4-fold improvement in these functions was observed compared to BAL devices entrapped with dispersed hepatocytes in collagen gels.

Receding cytochrome P450 activity in disassembling hepatocyte spheroids.

Primary rat hepatocytes can self-assemble to form multicellular spheroids when plated onto Primaria petri dishes or suspended in stirred vessels. These spheroids exhibit prolonged viability, enhanced liver-specific functions and differentiated ultrastructure compared to monolayer cultures. Upon transfer to collagen coated surface, or upon the addition of fetal bovine serum (FBS) to the culture, these spheroids began to disassemble and spread on the surface. The dynamics of cytochrome P450 CYP1A1/2 activity in the course of spheroid disassembly was examined in situ by detection of the fluorescent product, resorufin, of ethoxyresorufin O-dealkylation. Optical sectioning of the disassembling spheroids by confocal microscopy demonstrated that hepatocytes that reverted to monolayer exhibited markedly lower CYP1A1/2 activity than those that remained in a multilayered structure. This occurred whether the disassembly was caused by incubation with FBS-containing medium or by cultivation on a collagen-coated surface. When spheroids were cultured on the surface of agar, the disassembly process was retarded even in the presence of FBS. However, even in those intact spheroids, the exposure to FBS markedly decreased CYP1A1/2 activity. The decreased CYP1A1/2 activity was correlated to a diminished smooth endoplasmic reticulum as seen in the transmission electron micrograph. The results clearly demonstrate that the disassembly of hepatocyte spheroids led to decreased CYP1A1/2 activity. Furthermore, FBS contained a factor that caused CYP1A1/2 to decrease even in intact spheroids.

Enhanced cytochrome P450 IA1 activity of self-assembled rat hepatocyte spheroids.

Primary rat hepatocytes can self-assemble to form multicellular spheroids when plated onto Primaria petri dishes. Spheroids have been observed to exhibit enhanced liver-specific functions and differentiated ultrastructure compared to monolayer cultures on dry collagen. With confocal scanning laser microscopy, CYP1A1 activity was evaluated in situ by detecting resorufin. This highly fluorescent molecule is the P450-mediated product of 7-ethoxyresorufin O-dealkylation (EROD). Significantly higher P450 activity was observed in spheroids compared to monolayers on collagen upon induction with 50 microM beta-naphthoflavone (BNF), a CYP1A inducer. This was confirmed by measuring microsomal EROD activity. The distribution of CYP1A1 activity within spheroids was heterogeneous, with higher activity localized to the hepatocytes in the interior. During the process of spheroid formation, cells were initially seen to attach and spread out as a monolayer. This stage was associated with relatively low CYP1A1 activity. As cells formed multicellular structures and aggregated into spheroids, the level of CYP1A1 activity increased over time. At least a fivefold higher fluorescence intensity was observed in spheroids compared to that of monolayers maintained on collagen. The higher P450 activity within spheroids may be associated with their ability to maintain a greater degree of differentiation compared to monolayers. These studies demonstrate the potential of hepatocyte spheroids as a model system for investigating drug metabolism, tissue engineering, and tissue self-assembly.

Formation of porcine hepatocyte spheroids for use in a bioartificial liver.

Xenogeneic hepatocytes have recently been used in a bioartificial liver device as a potential short-term extracorporeal support of acute liver failure. Scaling up the system requires large quantities of viable and highly active cells. Hepatocytes grown as spheroids manifest higher metabolic activities for longer time periods as compared to those in monolayer cultures. Use of hepatocyte spheroids for application in a bioartificial liver can possibly alleviate the need of scaling up. Porcine hepatocytes when cultured under stirred conditions, from multicellular spheroids in a defined culture medium. Spheroids were formed 24 h after cell inoculation with an efficiency of 80-90% and a mean diameter of about 135 microns. Scanning electron microscopy revealed numerous microvilli projecting from the entire surface of the spheroids. Transmission electron microscopy revealed differentiated hepatocytes which displayed well-developed cytoplasmic structures separated by bile canaliculus-like structures. The morphological studies show a resemblance between cells in the spheroids and in the liver in vivo. Urea-genesis by spheroids was twice as active and was sustained for a longer culture period than that by hepatocytes cultured as monolayers. Preparation of porcine hepatocyte spheroids in an agitated vessel is simple efficient and reproducible. It will allow for preparation of large quantities of spheroids to be employed in a bioartificial liver device as well as in liver metabolism studies.

Formation and characterization of hepatocyte spheroids.

Several investigators have demonstrated that freshly harvested hepatocytes self-assemble into three-dimensional, compacted, freely suspended aggregates known as spheroids (1-3). These aggregates have smooth, undulating surfaces and average approx 120 µm in diameter. Hepatocyte spheroids exhibit enhanced liver-specific activities and prolonged viability, compared to cells maintained as a monolayer (4,5). Extensive cell-cell contacts, tight junctions, and microvilli-lined channels that resemble bile canaliculi have been observed between hepatocytes in spheroids (6,7). Thus, these cells appear to mimic the morphology and ultrastructure of an in vivo liver lobule. Reorganization of hepatocytes into these three-dimensional structures is hypothesized to contribute to their enhanced liver-specific functions. Because of their enhanced function and tissue-like ultrastructure, hepatocyte spheroids show great promise for use in tissue-engineering applications and drug metabolism studies.

Mechanistics of formation and ultrastructural evaluation of hepatocyte spheroids.

Freshly harvested rat hepatocytes form spheroids on uncoated positively charged polystyrene surfaces. Time lapse microscopy revealed that cell movement and reorganization were involved in spheroid formation. Ultrastructural evaluation using scanning and transmission electron microscopy indicated polarized cellular morphology and extensive cell-cell communication within spheroids. Bile canalicular structures were observed to surround each individual hepatocyte, forming an intricate three-dimensional continuous network of channels that appeared to end as pores/holes on the surface of the spheroid. The maintenance of differentiated cellular morphology coincided with preservation of hepatocyte viability and enhanced levels of tissue specific functions in spheroids.

Photodegradation of humic acids in the presence of hydrogen peroxide.

A batch photoreactor was used to evaluate the UV/H2O2 oxidation process for the removal of humic acids in water. A 450-W UV lamp with high-pressure mercury vapor was employed as the light source. The residues of humic acids and hydrogen peroxide were measured for assessment of process performance and understanding of process reaction behavior. The UV photolysis alone can play an important role in the degradation of humic acids. The presence of hydrogen peroxide was found to promote the degradation efficiency. However, excessive dosage of H2O2 does not further improve the degradation of humic acids. On the contrary, the lower the H2O2 dosage the higher the amount of humic acids which can be removed. Aeration with air does not favor the removal efficiency of humic acids as the oxidation lasts for a sufficiently long time. The presence of carbonate species deteriorates the humic acids' removal, whereas it results in a larger amount of H2O2 decomposition.

Biosorption of uranium(VI) by a mangrove endophytic fungus Fusarium sp. #ZZF51 from the South China Sea.

The uranium(VI) accumulation was studied in detail by using the biomass of mangrove endophytic fungus Fusarium sp.#ZZF51 from the South China Sea. The uranium(VI) biosorption process onto the tested fungus powders was optimized at pH 4.0, adsorption time 60 min, and uranium(VI) initial concentration 50 mg L-1 with 61.89% of removal efficiency. According to Fourier transform infrared spectra for the tested fungus before and after loaded with uranium(VI), the results showed that both of hydroxyl and carboxyl groups acted as the important roles in the adsorption process. In addition, the experimental data were analyzed by using parameter and kinetic models, and it was obtained that the Langmuir isotherm model and the pseudo-second-order kinetic model provided better correlation with the experimental data for adsorption of uranium(VI).

[Effects of N-ethyl perhexiline on His bundle electrogram in rabbits].

N-Ethyl perhexiline (NEP), a drug was synthesized for the first time by Department of Organic Chemistry, Faculty of Chemistry, Beijing University. The effects of NEP on the A-V conduction and intra ventricular conduction were studied in the anesthetized rabbits by recording His bundle electrogram (HBE) and electrocardiogram (ECG). NEP 3 mg.kg-1 iv prolonged A-H, P-R and R-R intervals. When NEP 6 mg.kg-1 was given, the above changes became more significant, with A-H interval from 52 +/- 7 to 65 +/- 9 ms, P-R interval from 65 +/- 6 to 76 +/- 8 ms, R-R interval from 207 +/- 9 to 230 +/- 9 ms, and H-V interval from 19 +/- 3 to 23 +/- 5 ms. The effects of NEP were similar to that of perhexiline, but the effects of NEP on A-H and P-R intervals were stronger. NEP 6 mg.kg-1 iv antagonized shortening effect of nicotinamide 0.5 g.kg-1 on A-H interval in rabbits. When isoproterenol 10 micrograms.kg-1 was given 3 min after NEP 6 mg.kg-1 iv, the A-H interval prolongation induced by NEP was greatly inhibited. The results suggested that the prolongation effects of NEP on A-H, P-R and R-R intervals would be the results of its calcium-channel blockade.

Growth of Azotobacter vinelandii on Soil Nutrients.

Azotobacter vinelandii cells grew well in a medium made from soil and distilled water which contained little or no carbohydrate. They utilized p-hydroxybenzoic acid and other phenolic acids, soil nitrogen, and water-soluble mineral substances. Seventeen soils which supported excellent growth of A. vinelandii contained 11 to 18 different phenolic acids each, including p-hydroxybenzoic, m-hydroxybenzoic, vanillic, p-coumeric, syringic, cis- and trans-ferrulic, and other unidentified aromatic acids. Three white, chalky "caliche" soils which were taken from areas where no plants grew failed to support the growth of A. vinelandii, and these contained no, two, and three phenolic acids, respectively. A. vinelandii did not fix nitrogen when growing in dialysates of soils which contained numerous phenolic acids. Growth was ample and rapid in most of the soils tested, but cell morphology was different from that usually seen in chemically defined, nitrogen-free media which contain glucose.

Surgical results of second-attempt radial keratotomy.

The safety, efficacy, and stability of second-attempt radial keratotomy were evaluated in 20 eyes of 12 patients from September 1, 1982, to August 31, 1983. The average amount of refractive error change was 1.89 diopters with 1.38 diopters of corneal curvature flattening. The effect of the second-attempt operation was about 60% that of the first-attempt operation. No significant surgical complications were observed in this study.

Characterization of the three-compartment gel-entrapment porcine hepatocyte bioartificial liver.

A hybrid bioartificial liver device supporting a large mass of cells expressing differentiated hepatocyte metabolic capabilities is necessary for the successful treatment of fulminant hepatic failure. The three-compartment gel-entrapment porcine hepatocyte bioartificial liver was designed to provide "bridge" support to transplantation or until native liver recovery is achieved for patients with acute liver failure. The device is an automated mammalian cell culture system supporting 6-7 x 10(9) porcine hepatocytes entrapped in a collagen matrix and inoculated into the capillary lumen spaces of two 100 kDa molecular mass cut-off hollow fiber bioreactors. Gel contraction recreates a small lumen space within the hollow fiber which allows for the delivery of a nutrient medium. This configuration supported hepatocyte viability and differentiated phenotype as measured by albumin synthesis, ureagenesis, oxygen consumption, and vital dye staining during both cell culture and ex vivo application. The hollow fiber membrane was also shown to isolate the cells from xenogenic immunoglobulin attack. The gel-entrapment bioartificial liver maintained a large mass of functional hepatocytes by providing a three-dimensional cell culture matrix, by delivering basal nutrients through lumen media perfusion, and by preventing rejection of the xenocytes. These features make this device a favorable candidate for the treatment of clinical fulminant hepatic failure.

Efficient assembly of rat hepatocyte spheroids for tissue engineering applications.

Freshly harvested primary rat hepatocytes cultivated as multicellular aggregates, or spheroids, have been observed to exhibit enhanced liver-specific function and differentiated morphology compared to cells cultured as monolayers. An efficient method of forming spheroids in spinner vessels is described. Within 24 h after inoculation, greater than 80% of inoculated cells formed spheroids. This efficiency was significantly greater than that reported previously for formation in stationary petri dishes. With a high specific oxygen uptake rate of 2.0 x 10(-9) mmol O(2)/cell/h, the oxygen supply is critical and should be monitored for successful formation. Throughout a 6-day culture period, spheroids assembled in spinner cultures maintained a high viability and produced albumin and urea at constant rates. Transmission electron microscopy indicated extensive cell-cell contacts and tight junctions between cells within spheroids. Microvilli-lined bile canaliculus-like channels were observed in the interior of spheroids and appeared to access the exterior through pores at the outer surface. Spheroids from spinner cultures exhibited at least the level of liver-specific activity as well as similar morphology and ultrastructure compared to spheroids formed in stationary petri dishes. Hepatocytes cultured as spheroids are potentially useful three-dimensional cell systems for application in a bioartificial liver device and for studying xenobiotic drug metabolism. (c) 1996 John Wiley & Sons, Inc.

Hollow fiber bioartificial liver utilizing collagen-entrapped porcine hepatocyte spheroids.

A xenogeneic hollow fiber bioreactor utilizing collagen-entrapped dispersed hepatocytes has been developed as an extracorporeal bioartificial liver (BAL) for potential treatment of acute human fulminant hepatitis. Prolonged viability, enhanced liver-specific functions, and differentiated state have been observed in primary porcine hepatocytes cultivated as spheroids compared to dispersed hepatocytes plated on a monolayer. Entrapment of spheroids into the BAL can potentially improve performance over the existing device. Therefore, studies were conducted to evaluate the feasibility of utilizing spheroids as the functionally active component of our hybrid device. Confocal microscopy indicated high viability of spheroids entrapped into cylindrical collagen gel. Entrapment of spheroids alone into collagen gel showed reduced ability to contract collagen gel. By mixing spheroids with dispersed cells, the extent of collagen gel contraction was increased. Hepatocyte spheroids collagen-entrapped into BAL devices were maintained for over 9 days. Assessment of albumin synthesis and ureagenesis within a spheroid-entrapment BAL indicated higher or at least as high activity on a per-cell basis compared to a dispersed hepatocyte-entrapment BAL device. Clearance of 4-methylumbelliferone to its glucuronide was detected throughout the culture period as a marker of phase II conjugation activity. A spheroid-entrapment bioartificial liver warrants further studies for potential human therapy. (c) 1996 John Wiley & Sons, Inc.

Development of a bioartificial liver employing xenogeneic hepatocytes.

Liver failure is a major cause of mortality. A bioartificial liver (BAL) employing isolated hepatocytes can potentially provide temporary support for liver failure patients. We have developed a bioartificial liver by entrapping hepatocytes in collagen loaded in the luminal side of a hollow fiber bioreactor. In the first phase of development, liver-specific metabolic activities of biosynthesis, biotransformation and conjugation were demonstrated. Subsequently anhepatic rabbits were used to show that rat hepatocytes continued to function after the BAL was linked to the test animal. For scale-up studies, a canine liver failure model was developed using D-galactosamine overdose. In order to secure a sufficient number of hepatocytes for large animal treatment, a collagenase perfusion protocol was established for harvesting porcine hepatocytes at high yield and viability. An instrumented bioreactor system, which included dissolved oxygen measurement, pH control, flow rate control, an oxygenator and two hollow fiber bioreactors in series, was used for these studies. An improved survival of dogs treated with the BAL was shown over the controls. In anticipated clinical applications, it is desirable to have the liver-specific activities in the BAL as high as possible. To that end, the possibility of employing hepatocyte spheroids was explored. These self-assembled spheroids formed from monolayer culture exhibited higher liver-specific functions and remained viable longer than hepatocytes in a monolayer. To ease the surface requirement for large-scale preparation of hepatocyte spheroids, we succeeded in inducing spheroid formation in stirred tank bioreactors for both rat and porcine hepatocytes. These spheroids formed in stirred tanks were shown to be morphologically and functionally indistinguishable from those formed from a monolayer. Collagen entrapment of these spheroids resulted in sustaining their liver-specific functions at higher levels even longer than those of spheroids maintained in suspension. For use in the BAL, a mixture of spheroids and dispersed hepatocytes was used to ensure a proper degree of collagen gel contraction. This mixture of spheroids and dispersed cells entrapped in the BAL was shown to sustain the high level of liver-specific functions. The possibility of employing such a BAL for improved clinical performance warrants further investigations.