Biomedical subjects

R Yu

Publications and source records attributed to R Yu.

At least 55 records · Page 3Linked to original sources

PubMed2000

Rapid turnover of calcium in the endoplasmic reticulum during signaling. Studies with cameleon calcium indicators.

HEK293 cells expressing the thyrotropin-releasing hormone (TRH) receptor were transfected with cameleon Ca(2+) indicators designed to measure the free Ca(2+) concentration in the cytoplasm, [Ca(2+)](cyt), and the endoplasmic reticulum (ER), [Ca(2+)](er). Basal [Ca(2+)](cyt) was about 50 nm; thyrotropin-releasing hormone (TRH) or other agonists increased [Ca(2+)](cyt) to 1 micrometer or higher. Basal [Ca(2+)](er) averaged 500 micrometer and fell to 50-100 micrometer over 10 min in the presence of thapsigargin. TRH consistently decreased [Ca(2+)](er) to 100 micrometer, independent of extracellular Ca(2+), whereas agonists for endogenous receptors generally caused a smaller decline. When added with thapsigargin, all agonists rapidly decreased [Ca(2+)](er) to 5-10 micrometer, indicating that there is substantial store refilling during signaling. TRH increased [Ca(2+)](cyt) and decreased [Ca(2+)](er) if applied after other agonists, whereas other agonists did not alter [Ca(2+)](cyt) or [Ca(2+)](er) if added after TRH. When Ca(2+) was added back to cells that had been incubated with TRH in Ca(2+)-free medium, [Ca(2+)](cyt) and [Ca(2+)](er) increased rapidly. The increase in [Ca(2+)](er) was only partially blocked by thapsigargin but was completely blocked if cells were loaded with 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. In conclusion, these new Ca(2+) indicators showed that basal [Ca(2+)](er) is approximately 500 micrometer, that [Ca(2+)](er) has to be >100 micrometer to support an increase in [Ca(2+)](cyt) by agonists, and that during signaling, intracellular Ca(2+) stores are continuously refilled with cytoplasmic Ca(2+) by the sarcoendoplasmic reticulum Ca(2+)-ATPase pump.

Animals↗

PubMed2000

Virulence gene regulation inside and outside.

Much knowledge about microbial gene regulation and virulence is derived from genetic and biochemical studies done outside of hosts. The aim of this review is to correlate observations made in vitro and in vivo with two different bacterial pathogens in which the nature of regulated gene expression leading to virulence is quite different. The first is Vibrio cholerae, in which the concerted action of a complicated regulatory cascade involving several transcription activators leads ultimately to expression of cholera toxin and the toxin-coregulated pilus. The regulatory cascade is active in vivo and is also required for maintenance of V. cholerae in the intestinal tract during experimental infection. Nevertheless, specific signals predicted to be generated in vivo, such as bile and a temperature of 37 degrees C, have a severe down-modulating effect on activation of toxin and pilus expression. Another unusual aspect of gene regulation in this system is the role played by inner membrane proteins that activate transcription. Although the topology of these proteins suggests an appealing model for signal transduction leading to virulence gene expression, experimental evidence suggests that such a model may be simplistic. In Streptococcus pyogenes, capsule production is critical for virulence in an animal model of necrotizing skin infection. Yet capsule is apparently produced to high levels only from mutation in a two-component regulatory system, CsrR and CsrS. Thus it seems that in V. cholerae a complex regulatory pathway has evolved to control virulence by induction of gene expression in vivo, whereas in S. pyogenes at least one mode of pathogenicity is potentiated by the absence of regulation.

Animals↗

PubMed2000

Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in androgen-independent prostate cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce cell death in a variety of transformed cells but spared the normal cells. In this study, we examined its potential against advanced prostate cancer cells. Treatment of PC-3 and DU145 cells with TRAIL caused a rapid apoptotic cell death, whereas tumor necrosis factor-alpha (TNF-alpha) is ineffective unless in the presence of the protein synthesis inhibitor cycloheximide. The induction of apoptosis by TRAIL in PC-3 cells was mediated by a death receptor, DR 4, and the downstream caspases. Treatment of PC-3 cells with TRAIL also activated c-Jun NH2-terminal kinase 1 (JNK1); however, inhibition of JNK1 activation by its dominant-negative mutant had little effect on TRAIL-induced apoptosis. Furthermore, TRAIL weakly stimulated nuclear factor kappaB activity in PC-3 cells. Interestingly, activation of nuclear factor kappaB pathway by pretreatment with TNF-alpha did not prevent the induction of apoptosis by TRAIL. These data indicate that TRAIL triggers apoptosis in advanced prostate cancer cells through the activation of caspase cascades, which appears to be independent of TNF-alpha- and JNK-mediated mechanisms.

Apoptosis↗

PubMed2000

Activation of p38 and c-Jun N-terminal kinase pathways and induction of apoptosis by chelerythrine do not require inhibition of protein kinase C.

Chelerythrine, a natural benzophenanthridine alkaloid, has been reported to mediate a variety of biological activities, including inhibition of protein kinase C (PKC). Here we report that chelerythrine induced time- and dose-dependent activation of JNK1 and p38 in HeLa cells, which was mediated the upstream kinases, MEKK1 and MKK4. However, treatment with two other potent and selective PKC inhibitors, GF-109203X and Gö6983, or down-regulation of PKC activity by prolonged treatment with phorbol 12-myristate 13-acetate had no effect on JNK1 and p38 activities. Furthermore, under the conditions where JNK1 and p38 were activated, we did not observe any significant inhibitory effect of chelerythrine on the activities of PKC isozymes present in HeLa cells. Interestingly, pretreatment with the antioxidants, N-acetyl-L-cysteine, dithiothreitol, and glutathione, impaired chelerythrine-induced JNK1 and p38 activation. In addition, chelerythrine induced apoptosis that was blocked by the antioxidants and the dominant-negative mutants of MEKK1, MKK4, JNK1, and p38. Together, these results uncover a novel biochemical property of chelerythrine, i.e. activation of MEKK1- and MKK4-dependent JNK1 and p38 pathways through an oxidative stress mechanism, which mediate the induction of apoptosis, but are independent of PKC inhibition.

Alkaloids↗

PubMed2000

Adenoviral Bak overexpression mediates caspase-dependent tumor killing.

One of the most promising strategies in cancer gene therapy is adenoviral transfer of proapoptotic genes. We therefore evaluated the novel strategy of adenovirally overexpressing the proapoptotic Bak gene. Our results showed marked apoptosis in cancer cells in vivo and in vitro after Bak gene transfer via a binary adenoviral vector system. This effect was not seen in a caspase 3-defective cell line (MCF-7) and was abrogated in Bak-sensitive tumors after administration of the caspase inhibitor z-DEVD-fmk. Our results suggest that adenoviral-mediated overexpression of Bak provides a novel therapeutic strategy for cancer therapy, but this process appears to be caspase dependent.

Adenoviridae↗

PubMed2000

p38 mitogen-activated protein kinase negatively regulates the induction of phase II drug-metabolizing enzymes that detoxify carcinogens.

Phase II drug-metabolizing enzymes, such as glutathione S-transferase and quinone reductase, play an important role in the detoxification of chemical carcinogens. The induction of these detoxifying enzymes by a variety of agents occurs at the transcriptional level and is regulated by a cis-acting element, called the antioxidant response element (ARE) or electrophile-response element. In this study, we identified a signaling kinase pathway that negatively regulates ARE-mediated gene expression. Treatment of human hepatoma HepG2 and murine hepatoma Hepa1c1c7 cells with tert-butylhydroquinone (tBHQ) stimulated the activity of p38, a member of mitogen-activated protein kinase family. Inhibition of p38 activation by its inhibitor, SB203580, enhanced the induction of quinone reductase activity and the activation of ARE reporter gene by tBHQ. In contrast, SB202474, a negative analog of SB203580, had little effect. Consistent with this result, interfering with the p38 kinase pathway by overexpression of a dominant-negative mutant of p38 or MKK3, an immediate upstream regulator of p38, potentiated the activation of the ARE reporter gene by tBHQ, whereas the wild types of p38 and MKK3 diminished such activation. In addition, inhibition of p38 activity augmented the induction of ARE reporter gene activity by tert-butylhydroxyanisole, sulforaphane, and beta-naphthoflavone. Thus, p38 kinase pathway functions as a negative regulator in the ARE-mediated induction of phase II detoxifying enzymes.

Animals↗

PubMed2000

Delayed "Choice" quantum eraser

We report a delayed "choice" quantum eraser experiment of the type proposed by Scully and Druhl (where the "choice" is made randomly by a photon at a beam splitter). The experimental results demonstrate the possibility of delayed determination of particlelike or wavelike behavior via quantum entanglement. The which-path or both-path information of a quantum can be marked or erased by its entangled twin even after the registration of the quantum.

Journal Article↗

PubMed2000

Activation of antioxidant-response element (ARE), mitogen-activated protein kinases (MAPKs) and caspases by major green tea polyphenol components during cell survival and death.

Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase II gene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 microM with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 microM to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP

Antioxidants↗

PubMed2000

Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis.

Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many may become important therapeutic drugs of the future.

Animals↗

PubMed2000

Production of eicosapentaenoic acid by a recombinant marine cyanobacterium, Synechococcus sp.

The eicosapentaenoic acid (EPA) synthesis gene cluster from an EPA-producing bacterium, Shewanella sp. SCRC-2738, was cloned into a broad-host range vector, pJRD215, and then introduced into a marine cyanobacterium, Synechococcus sp. NKBG15041c, by conjugation. The transconjugant cyanobacteria produced 3.7 +/- 0.2% (2.24 +/- 0.13 mg/L) EPA (n-3) and 2.5 +/- 0.2% (1.49 +/- 0.06 mg/L) eicosatetraenoic acid (n-3) of the total fatty acids when the cells were cultured at 23 degrees C at a light intensity of 1,000-1,500 Lux. The EPA and eico-satetraenoic acid contents of the cells were increased to 4.6 +/- 0.6% (3.86 +/- 1.11 mg/L) and 4.7 +/- 0.3% (3.86 +/- 0.82 mg/L), and 7.5 +/- 0.3% (1.76 +/- 0.10 mg/L) and 5.1 +/- 0.2% (1.19 +/- 0.06 mg/L) when they were cultured at low temperature (18 degrees C) and at lower light intensity (40 Lux), respectively.

Alteromonas↗

PubMed2000

A global optimization strategy for predicting alpha-helical protein tertiary structure.

We present a global optimization strategy that incorporates predicted restraints in both a local optimization context and as directives for global optimization approaches, to predict protein tertiary structure for alpha-helical proteins. Specifically, neural networks are used to predict the secondary structure of a protein, restraints are defined as manifestations of the network with a predicted secondary structure and the secondary structure is formed using local minimizations on a protein energy surface, in the presence of the restraints. Those residues predicted to be coil, by the network, define a conformational sub-space that is subject to optimization using a global approach known as stochastic perturbation that has been found to be effective for Lennard-Jones clusters and homo-polypeptides. Our energy surface is an all-atom 'gas phase' molecular mechanics force field, that is combined with a new solvation energy function that penalizes hydrophobic group exposure. This energy function gives the crystal structure of four different alpha-helical proteins as the lowest energy structure relative to other conformations, with correct secondary structure but incorrect tertiary structure. We demonstrate this global optimization strategy by determining the tertiary structure of the A-chain of the alpha-helical protein, uteroglobin and of a four-helix bundle, DNA binding protein.

Algorithms↗

PubMed2000

Reduction of liver Fas expression by an antisense oligonucleotide protects mice from fulminant hepatitis.

Aberrant apoptosis-mediated cell death is believed to result in a number of different human diseases. For example, excessive apoptosis in the liver can result in fulminant and autoimmune forms of hepatitis. We have explored the possibility that inhibition of Fas expression in mice would reduce the severity of fulminant hepatitis. To do this, we have developed a chemically modified 2'-O-(2-methoxy)ethyl antisense oligonucleotide (ISIS 22023) inhibitor of mouse Fas expression. In tissue culture, this oligonucleotide induced a reduction in Fas mRNA expression that was both concentration- and sequence-specific. In Balb/c mice, dosing with ISIS 22023 reduced Fas mRNA and protein expressions in liver by 90%. The ID50 for this response was 8-10 mg kg-1 daily dosing, and the reduction was highly dependent on oligonucleotide sequence, oligonucleotide concentration in liver, and treatment time. Pretreatment with ISIS 22023 completely protected mice from fulminant hepatitis induced by agonistic Fas antibody, by a mechanism entirely consistent with an oligonucleotide antisense mechanism of action. In addition, oligonucleotide-mediated suppression of Fas expression reduced the severity of acetaminophen-mediated fulminant hepatitis, but was without effect on concanavalin A-mediated hepatitis. Our results demonstrate that 2'-O-(2-methoxy)ethyl containing antisense oligonucleotides targeting Fas can exert in vivo pharmacological activity in liver, and suggest that oligonucleotide inhibitors of Fas may be useful in the treatment of human liver disease.

Animals↗

PubMed2000

Flat panel detector-based cone-beam volume CT angiography imaging: system evaluation.

Preliminary evaluation of recently developed large-area flat panel detectors (FPDs) indicates that FPDs have some potential advantages: compactness, absence of geometric distortion and veiling glare with the benefits of high resolution, high detective quantum efficiency (DQE), high frame rate and high dynamic range, small image lag (< 1%), and excellent linearity (approximately 1%). The advantages of the new FPD make it a promising candidate for cone-beam volume computed tomography (CT) angiography (CBVCTA) imaging. The purpose of this study is to characterize a prototype FPD-based imaging system for CBVCTA applications. A prototype FPD-based CBVCTA imaging system has been designed and constructed around a modified GE 8800 CT scanner. This system is evaluated for a CBVCTA imaging task in the head and neck using four phantoms and a frozen rat. The system is first characterized in terms of linearity and dynamic range of the detector. Then, the optimal selection of kVps for CBVCTA is determined and the effect of image lag and scatter on the image quality of the CBVCTA system is evaluated. Next, low-contrast resolution and high-contrast spatial resolution are measured. Finally, the example reconstruction images of a frozen rat are presented. The results indicate that the FPD-based CBVCT can achieve 2.75-lp/mm spatial resolution at 0% modulation transfer function (MTF) and provide more than enough low-contrast resolution for intravenous CBVCTA imaging in the head and neck with clinically acceptable entrance exposure level. The results also suggest that to use an FPD for large cone-angle applications, such as body angiography, further investigations are required.

Angiography↗

PubMed2000

Molecular mechanisms of butylated hydroxylanisole-induced toxicity: induction of apoptosis through direct release of cytochrome c.

Butylated hydroxyanisole (BHA), a commonly used food preservative, is reported to have anticarcinogenic properties in some animal models. However, the use of BHA as a chemopreventive agent against cancer in human has been challenged by the observation that BHA may exert toxic effect in some tissues of animals. Therefore, it is of great significance to understand the mechanism of BHA-induced toxicity. Here, we report that BHA induces apoptosis in freshly isolated rat hepatocytes. Treatment of hepatocytes with BHA also induced loss of mitochondrial transmembrane potential (Deltapsi(m)), cytochrome c, and activation of caspase-3, -8, and -9 but not caspase-1. Pretreatment with cyclosporin A, an agent that stabilizes mitochondrial permeability transition pore, inhibited BHA-induced loss of Deltapsi(m), cytochrome c release, caspase activation, and apoptosis. Interestingly, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone failed to prevent these mitochondrial events, although it blocked caspase activation and apoptosis. Furthermore, BHA-induced apoptosis appeared to be independent of formation of reactive intermediates, as evidenced by the lack of effects of antioxidants N-acetyl-L-cysteine and ascorbic acid. Indeed, direct incubation of BHA with isolated mitochondria triggered cytochrome c release. Thus, these results indicate that the cytotoxicity of BHA is due to the induction of apoptosis that is mediated by the direct release of cytochrome c and the subsequent activation of caspases.

Animals↗

PubMed2000

Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging.

The pituitary transforming gene, PTTG, is abundantly expressed in endocrine neoplasms. PTTG has recently been recognized as a mammalian securin based on its biochemical homology to Pds1p. PTTG expression and intracellular localization were therefore studied during the cell cycle in human placental JEG-3 cells. PTTG mRNA and protein expressions were low at the G1/S border, gradually increased during S phase, and peaked at G2/M, but PTTG levels were attenuated as cells entered G1. In interphase cells, wild-type PTTG, an epitope-tagged PTTG, and a PTTG-EGFP conjugate all localized to both the nucleus and cytoplasm, but in mitotic cells, PTTG was not observed in the chromosome region. PTTG-EGFP colocalized with mitotic spindles in early mitosis and was degraded in anaphase. Intracellular fates of PTTG-EGFP and a conjugate of EGFP and a mutant inactivated PTTG devoid of an SH3-binding domain were observed by real-time visualization of the EGFP conjugates in live cells. The same cells were continuously observed as they progressed from G1/S border to S, G2/M, and G1. Most cells (67%) expressing PTTG-EGFP died by apoptosis, and few cells (4%) expressing PTTG-EGFP divided, whereas those expressing mutant PTTG-EGFP divided. PTTG-EGFP, as well as the mutant PTTG-EGFP, disappeared after cells divided. The results show that PTTG expression and localization are cell cycle-dependent and demonstrate that PTTG regulates endocrine tumor cell division and survival.

Amino Acid Sequence↗

PubMed2000

[DNA polymorphism of Pvu II site in the lipoprotein lipase gene in patients with type 2 diabetes mellitus].

OBJECTIVE: To study the relationship between the lipoprotein lipase(LPL) gene and type 2 diabetes mellitus (DM) and its lipid metabolism. METHODS: PCR-RFLP method was used to determine the DNA polymorphism of 6th intron at LPL gene in 127 DM patients and 125 controls. RESULTS: The allele frequencies in case and control groups were 69.3%, 63.6% for "P+" and 30.7%, 36.4% for "P-", respectively; the frequencies of genotypes were 48.0%, 44.8% for P+/P+, 42.5%, 37. 6% for P+/P- and 9.45%, 17.6% for P-/P-, respectively. There was no significant difference in frequencies of genotypes or alleles between the two groups. The LPL Pvu II polymorphism in Chinese population was similar to that in Japanese population, and was different from that in European and American population. CONCLUSION: The LPL-Pvu II-RFLP in Chinese population is not significantly associated with type 2 diabetes mellitus. The significant difference of Pvu II-RFLP among various races was observed.

Adult↗

PubMed2000

[Imaging diagnosis for abdominal tuberculous lymphadenopathy].

OBJECTIVE: To evaluate the value of X-ray imaging for diagnosing abdominal tuberculous lymphadenopathy. METHODS: 27 cases of tuberculous lymphadenopathy proved by clinical or pathohistological evidence were collected, all of which were examined with radiological imaging methods. RESULTS: The typical CT findings enlarged lymph nodes with peripheral or multilocular enhancement. Enlarged lymph nodes with multiple flecked or massive calcifications were important for diagnosis. Ultrasound examination showed enlarged lymph nodes with uniform echo (less than 2 cm) and with heterogeneous echo (larger than 2 cm). The aim of the barium meal examination of the gastrointestinal tract was to find tuberculous lymphadenopathy encroaching on intestine or merged with intestinal tuberculosis. Abdominal X-ray plain film was helpful to find the calcified tuberculous lymphadenopathy and intestinal obstruction. CONCLUSIONS: Various imaging methods have shown their diagnostic value, but CT was the most important tool for definite diagnosis of tuberculous lymphadenopathy. Ultrasound was more useful for follow-up cases.

Adolescent↗

PubMed2000

[Quantitative evaluation of dyspnea and the effects of M-receptor antagonist on dyspnea in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To study the method of quantitative evaluation of dyspnea and to investigate the effects of M-receptor antagonist inhalation on dyspnea in patients with chronic obstructive pulmonary disease (COPD) during exercise. METHODS: Cycle exercise test was used in 27 patients with COPD and the effects of ipratropium bromide, a M-receptor antagonist, by inhalation on dyspnea and exercise capacity in the patients were observed. RESULTS: (1) Dyspnea index as Borg scale was closely correlated with oxygen uptake (V(O2)) during exercise in all the patients. Three variables for quantitative evaluation of dyspnea could be derived from the linear regression line. They were Borg scale slope (BSS), threshold load of dyspnea (TLD), and breakpoint load of dyspnea(BLD). (2) BSS was negatively correlated with forced expiratory volume in one second to forced vital capacity ratio (r = -0.519, P < 0.01) and diffusing capacity of the lungs for carbon monoxide (r = -0.497, P < 0.01) but positively correlated with residual volume/total lung capacity (r = 0.396, P < 0.05). (3) Inhalation of ipratropium bromide could significantly improve BSS [from (12.09 +/- 3.41) BS x L(-1) x min(-1) to (8.57 +/- 2.79) BS x L(-1) x min(-1), P < 0.01] and BLD [from (0.77 +/- 0.19) L/min to (0.81 +/- 0.14) L/min, P < 0.05] during exercise. CONCLUSIONS: (1) BSS, TLD and BLD could be used as reliable and convenient variables in quantitative evaluation of dyspnea in patients with COPD. BSS and BLD could to some extent reflect the severity of the disease. (2) M-receptor antagonists could alleviate dyspnea and increase exercise capacity in patients with COPD.

Adult↗