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K Hsu

Publications and source records attributed to K Hsu.

At least 19 recordsLinked to original sources
PubMed2001

Down-regulation of matrix Gla protein messenger RNA in human colorectal adenocarcinomas.

Matrix Gla protein (MGP) is a vitamin K-dependent extracellular matrix protein commonly found in a variety of tissues. In this study, we describe the potential use of MGP gene expression as the tumor marker of colorectal cancer. A decrease in expression of the MGP gene was also discovered in colorectal cancer using differential screening of cDNA libraries. The MGP expression in 80 human colorectal adenocarcinomas was quantified by a Northern blot analysis to better define the expression pattern of MGP in colorectal cancer. The expression of MGP mRNA was reduced in 63 of 80 (79%) colorectal adenocarcinomas (P<0.001) as compared to the mRNA in adjacent normal tissue, implying that a decrease in MGP expression is associated with colorectal cancer development. The proportion of tumors with downregulated expression of MGP was lower in Duke's A/B than Duke's C/D (34 of 47 versus 26 of 33, respectively) tumors and was lower in moderate differentiation than poor differentiation (44 of 64 versus 16 of 16, respectively). However, chi(2) analysis does not reveal any correlation between a loss of MGP expression and tumor progression or differentiation state. In conclusion, the downregulation of MGP mRNA generally occurs in colorectal adenocarcinomas. Although the role of MGP in cancer development is unknown, the reduced expression of MGP may be used to distinguish the normal colorectal cells from malignant cells.

Adenocarcinoma↗
PubMed2001

Molecular architecture of the voltage-dependent Na channel: functional evidence for alpha helices in the pore.

The permeation pathway of the Na channel is formed by asymmetric loops (P segments) contributed by each of the four domains of the protein. In contrast to the analogous region of K channels, previously we (Yamagishi, T., M. Janecki, E. Marban, and G. Tomaselli. 1997. Biophys. J. 73:195-204) have shown that the P segments do not span the selectivity region, that is, they are accessible only from the extracellular surface. The portion of the P-segment NH(2)-terminal to the selectivity region is referred to as SS1. To explore further the topology and functional role of the SS1 region, 40 amino acids NH(2)-terminal to the selectivity ring (10 in each of the P segments) of the rat skeletal muscle Na channel were substituted by cysteine and expressed in tsA-201 cells. Selected mutants in each domain could be blocked with high affinity by externally applied Cd(2)+ and were resistant to tetrodotoxin as compared with the wild-type channel. None of the externally applied sulfhydryl-specific methanethiosulfonate reagents modified the current through any of the mutant channels. Both R395C and R750C altered ionic selectivity, producing significant increases in K(+) and NH(4)(+) currents. The pattern of side chain accessibility is consistent with a pore helix like that observed in the crystal structure of the bacterial K channel, KcsA. Structure prediction of the Na channel using the program PHDhtm suggests an alpha helix in the SS1 region of each domain channel. We conclude that each of the P segments undergoes a hairpin turn in the permeation pathway, such that amino acids on both sides of the putative selectivity filter line the outer mouth of the pore. Evolutionary conservation of the pore helix motif from bacterial K channels to mammalian Na channels identifies this structure as a critical feature in the architecture of ion selective pores.

Amino Acid Sequence↗
PubMed2001

Protective effect of lipophilic antioxidants on phorbol-induced acute lung injury in rats.

OBJECTIVE: To determine whether the lipophilic antioxidant U-74389G can ameliorate the acute lung injury induced by phorbol myristate acetate (PMA) in our isolated lung model in rats, and to compare its activity with the intracellular enzymes superoxide dismutase (SOD) or catalase. DESIGN: Randomized, controlled study. SETTING: Animal-care facility procedure room. SUBJECTS: Forty-two adult male Sprague-Dawley rats each weighing 250-350 g. INTERVENTIONS: Typical acute lung injury was induced successfully by PMA during 60 mins of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability (measured by using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/body weight ratio, pulmonary arterial pressure, and the protein concentration of the bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Pretreatment with 1 mg of U-74389G significantly attenuated the acute lung injury induced by PMA, all parameters having decreased significantly (p <.001). The protective effect of U-74389G was dose dependent, but SOD (6,000 U/kg) or catalase (50,000 U/kg) exhibited no protective effect. CONCLUSIONS: U-74389G significantly ameliorates acute lung injury induced by PMA in rats.

Animals↗
PubMed2001

Zebrafish myelopoiesis and blood cell development.

The zebrafish (Danio rerio) animal model offers a unique opportunity to discover novel genes required for the control of normal vertebrate myeloid cell development. It is well suited for both developmental and genetic analyses: eg, genome-wide chemical mutagenesis screens have led to the identification of specific new genes affecting vertebrate erythropoiesis. Mutants defective in one or more hematopoietic functions will be useful as models of human disease and will assist in the elucidation of lineage-specific developmental programs. By using a combination of forward genetic mutagenesis screens and emerging strategies based on transgenic and antisense knockdown approaches, it should be possible to dissect the genetic programs that lead to myeloproliferative/myelodysplastic syndromes and to acute myeloid leukemia.

Animals↗
PubMed2000

Effect of a Chinese herbal medicine mixture on a rat model of hypercholesterolemic erectile dysfunction.

PURPOSE: We examine the effect of a Chinese herbal medicine mixture on erectile function in a rat model of hypercholesterolemic erectile dysfunction. MATERIALS AND METHODS: In this study 32, 3-month-old Sprague-Dawley rats were used. The 8 control animals were fed a normal diet and the remaining 24 were fed 1% cholesterol diet for 4 months. After 2 months herbal medicine was added to the drinking water of the treatment group of 16 rats but not the cholesterol only group of 8. Of the 16 rats 8 received 25 mg./kg. per day (group 1) and 8 received 50 mg./kg. per day (group 2) of Chinese herbal medicine mixture. Serum cholesterol levels were measured at 2 and 4 months. At 4 months erectile function was evaluated with cavernous nerve electrostimulation in all animals. Penile tissues were collected for electron microscopy, and to perform Western blot for endothelial nitric oxide synthase, neuronal nitric oxide synthase, basic fibroblast growth factor (bFGF) and caveolin-1. RESULTS: Serum cholesterol levels were significantly higher in animals fed the 1% cholesterol diet compared to controls at 2 and 4 months. Nevertheless, there was no significant difference among group 1 (145 +/- 30 mg./dl.), group 2 (157 +/- 20) and the cholesterol only group (143 +/- 15). Systemic arterial pressure was not significantly different between the animals that were fed the 1% cholesterol diet and the controls. During electrostimulation of the cavernous nerve peak sustained intracavernous pressure was significantly lower in the cholesterol only group (50 +/- 23 cm. H2O) compared to the control group. Conversely erectile function was not impaired in the herbal medicine treated rats. Electron microscopy showed many caveolae with fingerlike processes in the cavernous smooth muscle and endothelial cell membranes in control and treated rats but not in the cholesterol only group of rats. Western blot did not show a difference among groups in protein expression for endothelial nitric oxide synthase and neuronal nitric oxide synthase in penile tissue but caveolin-1 and bFGF protein expression was significantly higher in groups 1 and 2 than in the cholesterol only and control groups. CONCLUSIONS: Rats developed erectile dysfunction after being fed a 1% cholesterol diet for 4 months. Although serum cholesterol levels were similar in the cholesterol only rats and those treated with Chinese herbal medicine mixture, erectile response was significantly better in the treated group. The mechanism of the herbal medicine is unknown. High levels of bFGF and caveolin-1 expression in the treated group may protect the cavernous smooth muscle and endothelial cells from the harmful effect of high serum cholesterol.

Animals↗
PubMed1999

Effects of nitric oxide synthase inhibitors on systemic hypotension, cytokines and inducible nitric oxide synthase expression and lung injury following endotoxin administration in rats.

Endotoxin shock is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors and acute lung edema. A nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA) has been shown to be effective in reversing acute lung injury. In the present study, we evaluated the effects of NOS blockade by different mechanisms on the endotoxin-induced changes. In anesthetized rats, lipopolysaccharide (LPS, Klebsiella pneumoniae) was administered intravenously in a dose of 10 mg/kg. LPS caused sustained systemic hypotension accompanied by an eightfold increase of exhaled NO during an observation period of 4 h. After the experiment, the lung weight was obtained and lung tissues were taken for the determination of mRNA expressions of inducible NOS (iNOS), interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha-(TNF-alpha). Histological examination of the lungs was also performed. In the control group injected with saline solution, mRNA expressions of iNOS, IL-1beta and TNF-alpha were absent. Four hours after LPS, the mRNA expressions of iNOS and IL-1beta were still significantly enhanced, but TNF-alpha was not discernibly expressed. LPS also caused a twofold increase in lung weight. Pathological examination revealed endothelial damage and interstitial edema. Various NOS inhibitors were given 1 h after LPS administration. These agents included Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), a constitutive NOS and iNOS inhibitor; S, S'-1,4-phenylene-bis-(1,2-ethanedinyl) bis-isothiourea dihydrobromide (1,4-PBIT, 10 mg/kg), a relatively specific iNOS inhibitor, and dexamethasone (3 mg/kg), an inhibitor of iNOS expression. These NOS inhibitors all effectively reversed the systemic hypotension, reduced the exhaled NO concentration and prevented acute lung injury. The LPS-induced mRNA expressions of iNOS and IL-1beta were also significantly depressed by these NOS inhibitors. Our results suggest that NO production through the iNOS pathway is responsible for endotoxin-induced lung injury. Certain cytokines such as IL-1beta are possibly involved. These changes are minimized by NOS inhibitors through different mechanisms.

Animals↗
PubMed1999

Behavioral and neurochemical effects of the dopamine transporter ligand 4-chlorobenztropine alone and in combination with cocaine in vivo.

The current studies evaluated the novel diphenylmethoxytropane analog 4-chlorobenztropine (4-Cl-BZT), cocaine, and combinations of the two drugs for their abilities to stimulate locomotor activity, produce cocaine-like discriminative stimulus effects, and elevate extracellular dopamine (DA) in the nucleus accumbens (NAc) as measured by in vivo microdialysis. Peripherally administered cocaine was approximately twice as efficacious as 4-Cl-BZT as a locomotor stimulant and was behaviorally active at a lower dose than was 4-Cl-BZT. Cocaine also was more efficacious than 4-Cl-BZT in producing discriminative-stimulus effects in rats trained to discriminate i.p. injections of 10 mg/kg cocaine from saline. The time course of behavioral activation differed markedly between the two drugs, with much shorter onset and duration of locomotor stimulant effects for cocaine relative to 4-Cl-BZT. Similarly, i.p. cocaine (10 and 40 mg/kg) induced a pronounced, rapid, and short-lived increase in DA in the NAc, whereas i.p. 4-Cl-BZT was effective only at the higher dose and produced a more gradual, modest, and sustained (>/=2 h) elevation in accumbens DA. In contrast to i.p. administration, local infusion of 4-Cl-BZT (1-100 microM) into the NAc through the microdialysis probe elevated extracellular DA to a much greater extent than did local cocaine (nearly 2000% of baseline maximally for 4-Cl-BZT versus 400% of baseline for cocaine) and displayed a much longer duration of action than cocaine. However, when microinjected bilaterally into the NAc at 30 or 300 nmol/side, cocaine remained a more efficacious locomotor stimulant than 4-Cl-BZT. Finally, pretreatment with i.p. 4-Cl-BZT dose dependently enhanced the locomotor stimulant, discriminative stimulus effects, and NAc DA response to a subsequent low-dose i.p. cocaine challenge. The diphenylmethoxytropane analog also facilitated the emergence of stereotyped behavior and convulsions induced by high-dose cocaine. The current results demonstrate that DA transporter ligands that do not share the neurochemical and behavioral profiles of cocaine nevertheless may enhance the effects of cocaine in vivo.

Animals↗
PubMed1998

Electroacupuncture decreases c-fos expression in the spinal cord induced by noxious stimulation of the rat bladder.

PURPOSE: The present study investigated the effects of noxious stimulation of the lower urinary tract on neuronal fos protein expression in the spinal micturition center of rats and also examined the effects of electroacupuncture (EA) on fos expression induced by noxious stimulation of the lower urinary tract. MATERIALS AND METHODS: Experiments were conducted on 21 female Sprague-Dawley rats divided into four groups. Group 1 rats (n = 5) served as normal controls. Group 2 rats (n = 5) received EA at the Sanyinjiao acupoint. Group 3 animals (n = 6) were catheterized through the urethra and instilled with 1% acetic acid, and group 4 (n = 5) animals received EA 1 hour before 1% acetic acid instillation. All animals underwent arterial perfusion, laminectomy, and spinal cord removal. Spinal cords were sectioned and processed for immunohistochemical staining for fos protein. RESULTS: No fos protein was detected in any spinal neurons in normal control animals, and either none or few (0 to 4 cells/section) fos-immunoreactive (fos-IR) cells were seen in animals treated with EA. Noxious stimulation of the lower urinary tract with 1% acetic acid drastically increased the number of fos-IR neurons (30 to 127 cells/L6 section, mean 76.17+/-13.98; 28 to 77, cells/S1 section, mean 59+/-8.30; 7 to 35 cells/S2 section, mean 19.83+/-4.10). However, EA administered 1 hour before 1% acetic acid instillation significantly decreased the number of fos-IR neurons resulting from chemical irritation (0 to 50 cells/L6 section, mean 19.8+/-9.33; 0 to 47 cells/S1 section, mean 13.2+/-9.12; 0 to 37 cells/S2 section, mean 13.6+/-7.31). CONCLUSIONS: Our study demonstrates that bladder instillation with 1% acetic acid induces fos protein expression in the spinal micturition center of the rat and that electroacupuncture can reduce this expression. These results suggest a link between electroacupuncture and reduction in spinal neuronal cell activity.

Acetic Acid↗
PubMed1998

Protective agents used as additives in University of Wisconsin solution to promote protection against ischaemia-reperfusion injury in rat lung.

1. An intervention to reduce ischaemia-reperfusion lung injury will be an important advance in transplant medicine. Although the mechanisms associated with producing ischaemia-reperfusion endothelial injury have not been completely elucidated, many of the injury mediators have been studied in detail. While no single pharmacological therapy is likely to be totally effective in eliminating this complex injury, we have developed a mixture of agents that are known to block pathways involved in producing ischaemia-reperfusion-associated lung vascular injury.2. The present study modified University of Wisconsin solution (UW) by adding one of the protective agents prostaglandin E1 (PGE1), dexamethasone (Dex) or dibutyryl cAMP (Bt2-cAMP), or a combination of these, to the perfusate of rat lungs exposed to 4 h of cold ischaemia followed by 1 h of reperfusion. Nine modified UW solutions were studied: (1) UW+Dex, (2) UW+PGE1, (3) UW+Bt2-cAMP, (4) UW+Dexx3, (5) UW+PGE1x3, (6) UW+Bt2-cAMPx3, (7) UW+Dex+PGE1, (8) UW+Dex+Bt2-cAMP, (9) UW+PGE1+Bt2-cAMP. These solutions were utilized in individual experiments to assess haemodynamic changes, lung weight gain, the capillary filtration coefficient (Kfc) and pathology in all lungs.3. The results indicate that lung weight gain and Kfc values were significantly lower than with UW alone in groups 1, 2 and 3, which contained only one additional protective agent. In groups 4, 5 and 6, which contain three times the concentration of each protective agent, both Kfc and lung weight gain were similar to those measured in groups 1, 2 and 3, i.e. lungs were protected but the protection was not dose dependent. In groups 7, 8 and 9, which contained two protective agents, lung weight gain and Kfc were greatly reduced compared with UW alone. Histopathological studies showed similar decreases in the injury profiles of lungs.4. Although UW contains several antioxidant protective agents such as allopurinol and glutathione, it did not provide effective protection in our ischaemia-reperfusion lung injury model. UW modified with an additive of PGE1, Dex or Bt2-cAMP attenuated ischaemia-reperfusion injury. Furthermore, UW containing two of these protective agents augmented the protection. Among the modified solutions, it appears that UW+PGE1+Bt2-cAMP protects the lungs to a greater extent than all other solutions used in our study. We suggest that preservation solutions containing PGE1-Bt2-cAMP will provide additional protective effects to organs stored for transplantation.

Adenosine↗
PubMed1997

A highly conserved nucleotide in the Alu domain of SRP RNA mediates translation arrest through high affinity binding to SRP9/14.

Binding of the signal recognition particle (SRP) to signal sequences during translation leads to an inhibition of polypeptide elongation known as translation arrest. The arrest activity is mediated by a discrete domain comprised of the Alu portion of SRP RNA and a 9 and 14 kDa polypeptide heterodimer (SRP9/14). Although very few nucleotides in SRP RNA are conserved throughout evolution, the remarkable conservation of G24, which resides in the region of SRP9/14 interaction, suggests that it is essential for translation arrest. To understand the functional significance of the G24 residue, we made single base substitutions in SRP RNA at this position and analyzed the ability of the mutants to bind SRP9/14 and to reconstitute functional SRPs. Mutation of G24 to C reduced binding to SRP9/14 by at least 50-fold, whereas mutation to A and U reduced binding approximately 2- and 5-fold respectively. The mutant RNAs could nevertheless assemble into SRPs at high subunit concentrations. SRPs reconstituted with mutant RNAs were not significantly defective in translation arrest assays, indicating that the conserved guanosine does not interact directly with the translational machinery. Taken together, these results demonstrate that G24 plays an important role in the translation arrest function of SRP by mediating high affinity binding of SRP9/14.

Base Sequence↗
PubMed1997

Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: studies on the involvement of dopamine.

The effects of cocaine and d-amphetamine on extracellular glutamate and aspartate levels in the nucleus accumbens, prefrontal cortex, and striatum were studied by in vivo microdialysis in awake, freely moving rats. In the nucleus accumbens, glutamate levels were stimulated by cocaine (15-30 mg/kg, i.p.), GBR 12909 (15 mg/kg, i.p.), and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were not affected. The increase in nucleus accumbens glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with dopamine antagonists; haloperidol (0.2 mg/kg, i.p.), SCH 23390 (0.02 mg/kg, i.p.), and raclopride (1 mg/kg, i.p.), as well as local 6-OHDA lesions of the nucleus accumbens. In the prefrontal cortex, glutamate levels were stimulated by both cocaine (15-30 mg/kg, i.p.) and d-amphetamine (2 mg/kg, i.p.), while aspartate levels were moderately stimulated by d-amphetamine only. The increase in prefrontal cortex glutamate levels following cocaine (30 mg/kg) was calcium-dependent and was blocked by pretreatment with SCH 23390 (0.02 mg/kg, i.p.), but not haloperidol (0.2 mg/kg, i.p.) or raclopride (1 mg/kg, i.p.). In the striatum, glutamate and aspartate levels were not affected by either cocaine (15-30 mg/kg, i.p.) or d-amphetamine (2 mg/kg, i.p.). These findings demonstrate that stimulants enhance glutamate release in limbic brain structures, nucleus accumbens, and prefrontal cortex, but not extrapyamidal brain structures, striatum. Furthermore, the increase in glutamate release in the nucleus accumbens may be mediated by dopamine.

Amphetamine↗
PubMed1997

PGE1, dexamethasone, U-74389G, or Bt2-cAMP as an additive to promote protection by UW solution in I/R injury.

A method to reduce ischemia-reperfusion (I/R) injury can be an important criterion to improve the preservation solution. Although University of Wisconsin solution (UW) works as a lung preservation solution, its attenuation effect on I/R injury has not been investigated. We attempted to determine whether, by adding various protective agents, modified UW solutions will enhance the I/R attenuation by UW. We examined the I/R injury in an isolated rat lung model. Various solutions, e.g., physiological salt solution (PSS), UW, and modified UW solutions containing various protective agents such as prostaglandin E1, dexamethasone, U-74389G, or dibutyryl adenosine 3',5'-cyclic monophosphate were perfused individually to evaluate the I/R injury. Isolated rat lung experiments, with ischemia for 45 min, then reperfusion for 60 min, were conducted in a closed circulating system. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficient (Kfc), protein content of lavage fluid, concentration of cytokines, and lung histopathology were analyzed. Results showed that the acute I/R lung injury with immediate permeability pulmonary edema was associated with an increase in tumor necrosis factor-alpha (TNF-alpha) production. A significant correlation existed between TNF-alpha and Kfc (r = 0.8, P < 0.0001) and TNF-alpha and LWG (r = 0. 9, P < 0.0001), indicating that TNF-alpha is an important cytokine modulating early I/R injury. Significantly lower levels of Kfc, LWG, TNF-alpha, and protein concentration of lung lavage (P < 0.05) were found in the UW-perfused group than in the control group perfused with PSS. Modified UW promoted the protective effect of UW to further decrease Kfc, LWG, and TNF-alpha (P < 0.05). Histopathological observations also substantiated this evidence. In the UW+U-74389G group, bronchial alveolar lavage fluid contained lowest protein concentration. We conclude that the UW solution attenuates I/R injury of rat lung and that the modified UW solutions further enhance the effect of UW in reducing I/R injury. Among modified solutions, UW+U-74389G is the best. Further investigation of the improved effects of the modified UW solutions would be beneficial in lung transplantation.

Adenosine↗
PubMed1997

Interleukin-1 in ischemia-reperfusion acute lung injury.

Interleukin-1 (IL-1) is a proinflammatory cytokine produced by blood-borne and resident inflammatory lung tissue involved in the thrombotic occlusion of the pulmonary microcirculation and the increase of the vascular permeability following a wide variety of injuries and sepsis. The locally accentuated, organ-related activation of this cytokine seems to be responsible for the development of acute lung injury. The present study was conducted to determine if IL-1beta was produced in an ischemia-reperfusion (I/R) rat model subjected to lung injury. We measured sequential perfusate levels of IL-1beta by ELISA and we measured IL-1 gene expression in the rat lung tissue by a reverse-transcriptase polymerase chain reaction method. Little IL-1beta gene expression was observed in normal rat lung tissue. Perfusate IL-1beta slightly increased 2 h after induced ischemia and 3 h after reperfusion. IL-1beta gene expression rapidly increased as early as 30 min after ischemia and continued to increase for up to 120 min. IL-1beta gene expression was dramatically upregulated during reperfusion after cessation of ischemia, reached a peak at 1 h, and then gradually decreased (2 to 3 h) to near baseline levels. During ischemia, the increased IL-1 gene expression was not significantly different between the ventral and dorsal sites of the lung. However, IL-1 gene expression markedly increased on the dorsal part (the dependent site for a rat in a supine position) after reperfusion. From these results, it appears that IL-1 may have an important role in I/R lung injury.

Acute Disease↗
PubMed1997

Residual abnormalities of pulmonary function in asymptomatic young adult asthmatics with childhood-onset asthma.

We investigated the pulmonary function of male asthmatics with childhood-onset asthma. Our results revealed that adult asthmatics with mild symptoms apparently have abnormal pulmonary function. On the other hand, after a 3-6-month symptom-free period, and even after inhalation of bronchodilator, they still showed significant residual abnormalities in pulmonary function. Pulmonary function tests are very sensitive tools for the assessment of airway limitations during an acute asthmatic attack. However, these tests are not sensitive enough to detect residual abnormalities in asymptomatic asthmatics. Although the positive predictive rate for detecting small airway dysfunction in asymptomatic asthmatics is not high, FEF25-75 proved to be the best (63.2%) among the conventional pulmonary function parameters. We therefore suggest using FEF25-75 instead of FEV1 or peak flow rate in clinical practice for the conventional assessment of effectiveness of treatment, especially in the follow-up of asthmatic patients. More sensitive and simple tests are required in the future for detection of small airway dysfunction in asymptomatic asthmatics. Moreover, strict and early treatment of this abnormality with steroids is mandatory to prevent the formation of sequelae.

Adult↗
PubMed1997

Dibutyryl cAMP prevents increased vascular permeability caused by air embolism in isolated rat lungs.

BACKGROUND AND HYPOTHESIS: Venous gas bubbles are routinely detected in astronauts undergoing extravehicular activities at lower suit pressure. Venous air embolism increases the pulmonary arterial pressure and the vascular permeability leading to acute lung injury. In the present study we evaluated the protective effect of dibutyryl cAMP, aminophylline, and pentoxifylline on the pulmonary vasculatures after air embolism. METHOD: In isolated and perfused rat lungs, we induced air embolism by introducing air bubbles into the pulmonary artery. We measured the pulmonary arterial pressures and capillary pressure. Vascular permeability was determined by measuring the filtration coefficient (Kf) and the protein concentration in the lung lavage fluid. RESULTS: Air infusion caused pulmonary hypertension and increased vascular permeability, resulting in pulmonary edema. The Kf (in g.min-1.cm H2O-1.100 g-1) increased from 0.44 +/- 0.05 at baseline to 2.98 +/- 0.47 after air infusion. Pretreatment with DBcAMP prevented the increase in Kf (0.63 +/- 0.09) caused by air embolism without altering the hemodynamics. Aminophylline and pentoxifylline did not prevent lung injury induced by air embolism. Although aminophylline did not alter the response of pulmonary arterial pressure to air infusion, it elevated the capillary pressure to 5.1 +/- 0.4 mmHg, which was significantly greater than that in the lung receiving air infusion alone. CONCLUSION: Our results suggest that DBcAMP prevents the increase in vascular permeability caused air embolism. The ineffectiveness of aminophylline and pentoxifylline on the prevention of air embolism-induced lung injury remains for further investigation.

Aerospace Medicine↗
PubMed1996

Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells.

Nearly 1 000 000 copies of Alu interspersed elements comprise approximately 5% of human DNA. Alu elements cause gene disruptions by a process known as retrotransposition, in which dimeric Alu RNA is a presumed intermediate. Dimeric Alu transcripts are labile, giving rise to stable left monomeric scAlu RNAs whose levels are tightly regulated. Induction of Alu RNA by viral infection or cell stress leads to a dramatic increase in dimeric Alu transcripts, while scAlu RNA increases modestly. Each monomer of the dimeric Alu element shares sequence homology with the 7SL RNA component of the signal recognition particle (SRP). The SRP protein known as SRP9/14 is also found in a discrete complex with scAlu RNA, although whether dimeric Alu RNA is associated with SRP9/14 had been unknown. Here we show that antiserum to human SRP9 immunoprecipitates both scAlu RNA and dimeric Alu RNAs and that these RNPs accumulate after adenovirus infection, while levels of SRP9, SRP14, SRP54 and 7SL SRP RNA are unaffected. Dimeric Alu RNAs are also associated with the La protein, indicating that these are indeed nascent RNA polymerase III transcripts. This report documents that induced Alu transcripts are assembled into SRP9/14-containing RNPs in vivo while SRP levels are unchanged. Implications for Alu RNA metabolism and evolution are discussed.

Adenoviruses, Human↗