Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice.

CONTEXT: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet. OBJECTIVES: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice. MATERIALS AND METHODS: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group. RESULTS: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P > 0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P < 0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P < 0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P < 0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group. DISCUSSION AND CONCLUSIONS: These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.

[Clinical analysis of diffusive interstitial lung diseases with positive anti-neutrophil cytoplasmic antibody].

OBJECTIVE: To explore the features of pulmonary interstitial pathological changes in diffuse interstitial lung disease (DILD) patients with positive anti-neutrophil cytoplasmic antibody (ANCA), and the similarities as well as differences between ANCA positive patients with non-primary vasculitis and primary systematic vasculitis. METHODS: Clinical data of 122 patients with DILD having ANCA examined from October 1995 to September 2008, were reviewed. Among the ANCA positive patients with non-primary vasculitis (Group A), those with primary systematic vasculitis (Group B), and the ANCA negative patients (Group C), the results of syndromes, signs, radiological manifestations, pulmonary function tests, bronchoscope examinations, bronchoalveolar lavage fluid (BALF) cytology and other laboratory examinations were compared. RESULTS: In the 122 DILD patients with ANCA results, 36 patients' ANCA (29.51%) were positive. The numbers of patients in Groups A, B, and C were 7, 29, and 86. Total lung capacity (TLC) decreased less and pleural pathological changes were more seen in Groups A and B than in Group C. Oliguria, haematuria, proteinuria, anaemia, and renal inadequacy in Group A, which were similar in Group C, appeared less than in Group B. Results of bronchoscope examination, BALF cytology, anti-nuclear antibody (ANA), and etc. were not significantly different among the three groups. CONCLUSION: In DILD patients, pulmonary interstitial changes of those with positive ANCA accompany with more pleural pathological changes and TLC decreased less than those with negative ANCA. In patients with positive ANCA, non-primary vasculitis had some similar clinical manifestations as primary systematic vasculitis, however, anaemia and renal damages were less seen in the non-primary vasculitis patients.

[The changing patterns and the associated factors of microbial pathogens in ventilator-associated pneumonia in a respiratory intensive care unit from 1995 to 2004].

OBJECTIVE: To investigate the changing patterns and associated factors of microbial pathogens which caused ventilator-associated pneumonia (VAP) in our respiratory intensive care unit (RICU) from 1995 to 2004. METHODS: Cases of VAP in our RICU from 1995 to 2004 (n = 137) were retrospectively analyzed, 47 cases from 1995 to 1999 and 90 cases from 2000 to 2004. VAP was diagnosed according to the following criteria: pneumonia occurred 48 hours after tracheal intubations; new or progressive infiltrative opacities on chest X ray film; and at least two of the following clinical features: (1) Temperature > 38.0 degrees C or < 35.5 degrees C, (2) WBC > 10 x 10(9)/L or < 4 x 10(9)/L, (3) purulent airway secretions; and positive bacterial cultures (the samples obtained through endotracheal intubations). The data were analyzed using statistical software SPSS version 11.5. Continuous data were expressed as (-x) +/- s. t-test and chi(2)-test were used for continuous and categorical data, respectively. Logistic regression analysis was used to determine the risk factors for special pathogens. RESULTS: The mean incidence of VAP was 17.9% from 1995 to 2004 (137/765), 16.2% from 1995 to 1999 (n = 47, 3.1% - 29.8%) and 19.6% from 2000 to 2004 (n = 90, 12.4% - 27.7%). From 1995 to 1999, common pathogens were Stenotrophomonas maltophilia (n = 15, 23.4%), Pseudomonas aeruginosa (n = 12, 18.8%), Aerobacter cloacae (n = 8, 12.5%) and Acinetobacter baumanii (n = 7, 10.9%). From 2000 to 2004, common pathogens were Acinetobacter baumanii (n = 40, 34.2%), Pseudomonas aeruginosa (n = 32, 27.4%), Staphylococcus aureus (n = 24, 20.5%) and Stenotrophomonas maltophilia (n = 8, 6.8%). There were 2 cases (2/64, 3.1%) caused by Staphylococcus aureus from 1995 to 1999, and both were caused by Methicillin-resistant Staphylococcus aureus (MRSA); there were 24 cases caused by Staphylococcus aureus from 2000 to 2004, and 21 cases (21/117, 17.9%) were caused by MRSA.There were 11 (11/47, 23.4%) and 45 (45/90, 50.0%) cases with central intravenous catheters in the period of 1995 to 1999 and 2000 to 2004, respectively. In the period of 1995 to 1999 and 2000 to 2004, durations of aerosolized therapy were (46 +/- 55) and (28 +/- 30) days. There were 12 patients (12/47, 25.5%) using second-generation cephalosporin before VAP occurred in the period of 1995 to 1999 and 7 patients (7/90, 7.8%) in the period of 2000 to 2004. There were 13 patients (13/47, 27.7%) using penicillin before VAP in the period of 1995 to 1999 and 10 patients (10/90, 11.1%) in the period of 2000 to 2004. There were 10 patients (10/47, 21.3%) using quinolones before VAP in the period of 1995 to 1999 and 46 patients (46/90, 51.1%)in the period of 2000 to 2004. The occurrence of Staphylococcus aureus VAP may be related to the cross-infection between inpatients (Wald = 16.690, P < 0.01, OR = 9.212). VAP caused by Stenotrophomonas maltophilia was positively related to duration of aerosolized therapy (Wald = 7.852, P < 0.01, OR = 1.021). VAP caused by Acinetobacter baumanii was positively related to third-generation cephalosporin usage (Wald = 5.553, P < 0.05, OR = 3.461). CONCLUSIONS: The incidence of VAP was not increased in the recent 10 years in our RICU, but the incidence of VAP caused by Acinetobacter baumanii. Staphylococcus aureus and MRSA increased significantly, may be related to the decrease of duration of aerosolized therapy, the usage of different kinds of antibiotics and cross-infection between inpatients.

[Pleural sarcoidosis: report of cases and review of the literature].

OBJECTIVE: To analyze the clinical features and differential diagnosis of pleural disease caused by sarcoidosis. METHODS: The clinical data of cases of sarcoidosis diagnosed with pathological evidence in this hospital were retrospectively analyzed. The clinical features and the diagnostic procedures of the cases with pleural disease as the main manifestations were reported. A review of case reports and series published in Chinese literature were carried out to study the incidence and the features of pleural effusion and pneumothorax in sarcoidosis. RESULTS: Thirty-two cases of pulmonary sarcoidosis were diagnosed with pathological evidence, of which 2 cases (2/32, 6.3%) presented as pleural effusion with one confirmed by medical thoracoscopy; one case (1/32, 3.1%) presented as recurrent pneumothorax and interstitial lung disease, and the diagnosis was confirmed by open lung biopsy. Pleural fluid analysis showed exudates with lymphocyte predominance. The fluid level of adenosine deaminase (ADA) was all less than 30 U/L and increased angiotensin converting enzyme level was demonstrated in one case. All 3 cases had been misdiagnosed as tuberculosis and received anti-tuberculous therapy for a period of 1 - 12 months. A review of the case reports and series in Chinese literature showed that the incidence of pleural disease in sarcoidosis was 3.4% - 16.7% in different series, and that pleural effusion in sarcoidosis was misdiagnosed as tuberculous in most cases. CONCLUSIONS: Pleural sarcoidosis is not rare in Chinese patients, but often misdiagnosed as tuberculous pleural disease. Recognition of this fact is of clinical importance both in the diagnosis of sarcoidosis and in the differential diagnosis of pleural diseases.

Endogenous hydrogen sulfide in patients with COPD.

OBJECTIVES: COPD is characterized by progressive airway obstruction. Recent studies showed that besides nitric oxide (NO) and carbon monoxide (CO), endogenous hydrogen sulfide (H(2)S) might be the third signaling gasotransmitter. To clarify the role of endogenous H(2)S in the pathogenesis of COPD, we investigated the relation of serum H(2)S level to severity of COPD as defined by lung function and airway inflammation. METHODS: Levels of serum H(2)S and NO, lung function, and cell differential counts in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD, and 13 healthy subjects. Patients with AECOPD had arterial blood gas levels measured and underwent Doppler echocardiography. In addition, in order to clarify the effects of age and smoking status on serum H(2)S level, we recruited three groups who were age matched to the study group but had no airflow limitation (59 subjects). RESULTS: Serum H(2)S level (34.0 +/- 0.9 to 36.4 +/- 1.1 micromol/L [+/- SEM]) did not differ among healthy control subjects with different ages (56.6 to 75.0 years, respectively). Serum H(2)S level was significantly higher in patients with stable COPD than in patients with AECOPD and age-matched control subjects (p < 0.01) and correlated positively with NO level in all healthy control subjects and all patients with COPD (r = 0.352, p = 0.000). Serum H(2)S level was significantly lower in smokers than nonsmokers, both with AECOPD (p < 0.05) and healthy control subjects (p < 0.01). It was significantly lower in smokers with AECOPD than healthy smokers and smokers with stable COPD (p < 0.01). Serum H(2)S level differed and was decreased (p < 0.05) among stable COPD patients by stage of airway obstruction (p < 0.05), and it was lower in patients with stage III than stage I obstruction (p < 0.05). Serum H(2)S level in all patients with COPD and healthy control subjects correlated positively with the percentage of predicted FEV(1) value (r = 0.300, p = 0.009). It was lower in patients with AECOPD and systolic pulmonary artery pressure (PASP) > or = 35 mm Hg than those with PASP within the normal range (< 35 mm Hg) [p < 0.05] and was negatively correlated with PASP (r = - 0.561, p = 0.011). Serum H(2)S level was negatively correlated with proportion of neutrophils in sputum (r = - 0.422, p = 0.001) and positively correlated with proportion of lymphocytes (r = 0.286, p = 0.028) and macrophages (r = 0.334, p = 0.01) in all patients with COPD. CONCLUSIONS: Endogenous H(2)S is involved in the pathogenesis of airway obstruction in COPD, and its alteration in level may be connected with disease activity and severity.

Association of gene polymorphisms of tumour necrosis factor-alpha and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing.

BACKGROUND: Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-alpha (TNF-alpha) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-alpha and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-alpha gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population. METHODS: A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-alpha gene-308 position. The products were investigated by sequence analysis also. RESULTS: One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P = 0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62 - 25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR = 7.7 (95% CI 1.37 - 43.80). The frequencies of A allele in the TNF-alpha gene were 5.9% in COPD and 3.1% in controls (P = 0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD. CONCLUSIONS: There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-alpha between Han Chinese patients with COPD versus control. Thus, it does not appear that these SNPs are independent factors in COPD for Han nationality in Beijing. However, these SNPs may increase the risk of COPD among smokers.

[Cross-talk between calcineurin and protein kinases in airway remodeling in asthma].

OBJECTIVE: To determine the role of cross-talk between calcineurin-dependent signal transduction pathway and protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) in airway remodeling in asthma. METHODS: Male guinea pigs were sensitized with intraperitoneal injections of ovabumin (OVA), then treated with cyclosporin A (CsA, 5 mg/kg), an inhibitor of calcineurin, then inhaled OVA for 2 weeks 14 days later. Activities of calcineurin, PKC, MAPK, and PKA were was analyzed by phosphorylation and dephosphorylation. In primary cultures of rat airway smooth muscle cells (ASMC), activities of calcineurin, PKC, MAPK, and cross-talk induced by urotensin II (UII ), a recently identified strong mitogen, were measured. RESULTS: (1) The activities of calcineurin, MAPK and PKC increased by 19% (P<0.01), 28% (P<0.01) and 35% (P<0.05), respectively, in the asthmatic group compared with controls but decreased by 52% (P<0.01), 18% (P<0.05) and 52% (P<0.01), respectively, in the CsA group compared with asthmatic group. PKA activity in the asthma group decreased by 53% (P<0.01) compared with controls but increased by 2.65-fold (P<0.01) in the CsA group compared with the asthma group. (2) UII 10(-7) mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P<0.01), respectively, after incubating for 20 min. It increased CaN activity in a time-dependent manner, being 1.67 times that of the control for 24 h (P<0.01). (3) CsA 10(-6) mol/L and H(7) 50 micromol/L, an inhibitor of PKC, inhibited UII-stimulated CaN activity by 45% (P<0.01) and 21% (P<0.05), respectively, while PD(98059) 50 micromol/L, an inhibitor of MAPK, had no effect on CaN activity (P>0.05). (4) CsA 10(-6) mol/L inhibited UII-stimulated PKC activity by 14% (P<0.05), while having no effect on MAPK activity (P>0.05). CONCLUSION: The signal transduction pathways between calcineurin and other protein kinases such as PKC, MAPK and PKA have cross-talk in airway remodeling in asthma.

[Epidemiological data of chronic obstructive pulmonary disease in Yanqing County in Beijing].

OBJECTIVE: To evaluate the epidemiological characteristic and risk factors of chronic obstructive pulmonary disease (COPD) in the rural area of Beijing. METHODS: The data of 1,624 people aged more than 40 in 5 villages in Yanqing County in Beijing were collected. The habitation condition, life and cooking habit, smoking history, personal history and family history were asked, and their physical examinations and lung function tests were conducted. RESULTS: The prevalence of COPD was 9.11% in this area, 15.05% in males and 3.76% in females. There were significant differences in sex, age, smoking history, family history, frequent cough before age 14 and body index between the COPD and non-COPD groups. The prevalence of corpulmonale was 1.66% in this area. CONCLUSION: The prevalence of COPD was high in this area and related with sex, age, smoking history, family history, frequent cough before age 14 and low body index. Other factors such as environment, working exposure need to be studied in the future. COPD is a major public health problem, which should claim more attention.

[The investigation of genotype and expression of alpha1-AT in patients with COPD].

OBJECTIVE: To detect genotype and expression of alpha1-AT in the patients with COPD to investigate the effect of alpha1-AT on pathogenesis of COPD. METHODS: Detection of PiZ allele in exon V and S allele in exon III were performed by PCR-Amplification of Specific Allele (PASA). The levels of serum alpha1-AT in some of subjects were measured by Enzyme-Linked Immunoadsordent Assay (ELISA). RESULTS: The PCR production of S mutation was 285 base pair fragment. The PCR production of Z-mutation was 250 base pair fragment. The results showed that All subjects were PiMM genotype of alpha1-AT, including COPD and control group. The mean serum alpha1-AT concentration, in patients with COPD, was 2.3 g/L +/- 1.1 g/L. In control group, the mean serum alpha1-AT concentration was 2.7 g/L +/- 0.84 g/L. The levels of alpha1-AT in patients with COPD are significantly lower than that in control group (P = 0.012). RV/TL and degree of pursiness are negative correlation with the levels of alpha1-AT. The r value were -0.208 and -0.262 respectively. CONCLUSION: There was no difference in genetic polymorphism of alpha1-AT between the patients with COPD and controls. However, the levels of serum alpha1-AT were significantly lower in the patients with COPD compared with control subjects. alpha1-AT deficiency may be a factor of the pathogenesis of COPD. The mechanism of alpha1-AT deficiency needs to be addressed.

[Endogenous hydrogen sulfide in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the role of endogenous hydrogen sulfide (H(2)S) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Levels of serum H(2)S and nitric oxide (NO), lung function and cell differential count in induced sputum were studied in 27 patients with acute exacerbation of COPD (AECOPD), 37 patients with stable COPD and 13 health subjects. Echo-Doppler assessment and arterial blood gas were measured in patients with AECOPD. RESULTS: (1) The serum H(2)S level was significantly higher in patients with stable COPD [(50.8 +/- 2.5) micromol/L] as compared to those in the controls [(39.8 +/- 1.6) micromol/L] and in patients with AECOPD [(33.5 +/- 2.2) micromol/L, P < 0.01]. (2) The level of serum H(2)S was significantly lower in smokers with AECOPD [(28.1 +/- 1.3) micromol/L] as compared to nonsmokers with AECOPD [(39.4 +/- 3.9) micromol/L, P < 0.05] and healthy nonsmokers [(39.8 +/- 1.6) micromol/L, P < 0.01]. (3) There was significant difference in the serum H(2)S level among stable COPD patients with different severity of airway obstruction (P < 0.05); being lower in patients with stage III [(45.1 +/- 4.1) micromol/L] as compared to stage I obstruction [(70.2 +/- 6.2) micromol/L, P < 0.05]. (4) AECOPD with pulmonary hypertension pulmonary artery systolic pressure (PASP) > or = 35 mm Hg (1 mm Hg = 0.133 kPa) showed a lower serum H(2)S level [(26.3 +/- 2.2), (36.2 +/- 2.5) micromol/L, P < 0.05] than that with a normal resting PASP. (5) H(2)S in serum was positively correlated with NO levels (r = 0.278, P = 0.029), FEV(1)% predicted values (r = 0.533, P = 0.000), percentage of sputum lymphocytes (r = 0.286, P = 0.028) and macrophages (r = 0.334, P = 0.01); and negatively correlated with PASP (r = -0.561, P = 0.011) and the percentage of sputum neutrophils (r = -0.422, P = 0.001) in patients with COPD. CONCLUSION: Endogenous H(2)S may be involved in the pathogenesis of airway obstruction in COPD and may be a noninvasive marker of disease activity and severity.

[Characteristics of non-symptomatic chronic obstructive pulmonary disease patients].

OBJECTIVE: To evaluate the epidemiological characteristics of non-symptomatic chronic obstructive pulmonary disease (COPD) patients in a rural area in Beijing. METHODS: The data of 1,624 people aged more than 40 in 5 villages in Yanqing county in Beijing were collected. Information of medical history and symptom were obtained, and physical examination and lung function test were performed. RESULTS: The prevalence of COPD was 9.1% (148/1 624) in this area. In these 148 patients, 62 (42%) were non-symptomatic and 86 (58%) were symptomatic, the prevalence of non-symptomatic COPD being 3.8% (62/1 624). There was no statistical difference in the sex, age, occupation, marriage status, education level and smoking index between the symptomatic and the non-symptomatic groups (all P > 0.05). The forced expired volume in one second (FEV(1)) and FEV(1)% predicted were lower in the symptomatic group [(1.3 +/- 0.7) L, (61 +/- 23)%] than those in the non-symptomatic group [(1.5 +/- 0.6) L, (70 +/- 22)%; all P < 0.05]. CONCLUSIONS: The prevalence of COPD was high in this area with a high percentage of non-symptomatic patients. The COPD prevalence might be underestimated due to the symptom free patients.

The role of calcineurin in the lung fibroblasts proliferation and collagen synthesis induced by basic fibroblast growth factor.

OBJECTIVE: To investigate the role of calcineurin (CaN) in the lung fibroblast proliferation and collagen synthesis induced by basic fibroblast growth factor (bFGF). METHODS: We used Western blot and immunohistochemical methods for investigating the content and distribution of calcineurin in the lung tissue. Calcineurin activity in different tissues was measured using (32)P-labelled substrate. In the primary culture of lung fibroblasts, (3)H-thymidine ((3)H-TdR) and (3)H-proline incorporation methods were used to study the effect of cyclosporin A (CsA), an inhibitor of calcineurin, on the lung fibroblast DNA and collagen synthesis stimulated by bFGF. RESULTS: We found that calcineurin was expressed in lung tissue and has phosphatase activity (7.1 +/- 2.0 pmol Pi/mg pr/min). CsA (10(-8) - 10(-6) mol/L) inhibited lung fibroblast (3)H-TdR incorporation induced by bFGF in a dose-dependent manner, with the inhibitory rates by 20%, 46% and 66% (P < 0.01). CsA (10(-7) - 10(-6) mol/L) inhibited (3)H-proline incorporation in lung fibroblasts stimulated by bFGF, with the inhibitory rates by 21% and 37% (P < 0.01). In a culture medium, CsA (10(-8) - 10(-6) mol/L) inhibited (3)H-proline secretion induced by bFGF in a dose-dependent manner, with the inhibitory rates by 19%, 29% (P < 0.05) and 56% (P < 0.01). CsA (10(-7) mol/L) could inhibit calcineurin activity by 44% in lung fibroblasts (P < 0.01). CONCLUSIONS: Calcineurin is expressed in lung tissue and has phosphatase activity. It is involved in the bFGF stimulated lung fibroblast DNA and collagen synthesis.

The signal transduction pathway in the proliferation of airway smooth muscle cells induced by urotensin II.

BACKGROUND: Human urotensin II (UII) is the most potent mammalian vasoconstrictor identified so far. Our previous study showed that UII is a potent mitogen of airway smooth muscle cells (ASMC) inducing ASMC proliferation in a dose-dependent manner. The signal transduction pathway of UII mitogenic effect remains to be clarified. This study was conducted to investigate the signal transduction pathway in the proliferation of ASMC induced by UII. METHODS: In primary cultures of rat ASMCs, activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and calcineurin (CaN) induced by UII were measured. The effect of CaN on PKC and MAPK was studied by adding cyclosporin A (CsA), a specific inhibitor of CaN. Using H7 and PD98059, inhibitors of PKC and MAPK, respectively, to study the effect of PKC and MAPK on CaN. The cytosolic free calcium concentration induced by UII was measured using Fura-2/AM. RESULTS: UII 10(-7) mol/L stimulated ASMC PKC and MAPK activities by 44% and 24% (P < 0.01), respectively, after incubating for 20 minutes. It increased CaN activity in a time-dependent manner, being 1.68 times as that of control for 24 hours (P < 0.01). It promoted the cytosolic free calcium concentration increase of 18% (P < 0.01). CsA 10(-6) mol/L and H7 50 micromol/L inhibited UII-stimulated CaN activity by 45% (P < 0.01) and 21% (P < 0.05), respectively, while PD98059 50 micromol/L had no effect on CaN activity (P > 0.05). CsA 10(-6) mol/L inhibited UII-stimulated PKC activity by 14% (P < 0.05), while having no effect on MAPK activity (P > 0.05). CONCLUSIONS: UII increases cytosolic free calcium concentration and activates PKC, MAPK and CaN. The signal transduction pathway between PKC and CaN has cross-talk.

Clinical diagnostic approach to severe acute respiratory syndrome: an institution's experience.

OBJECTIVE: To analyze diagnostic approach to severe acute respiratory syndrome (SARS) according to the diagnostic criteria issued by the Ministry of Health of China (MHC). METHODS: The clinical data and the diagnostic results of 108 cases of SARS were retrospectively reviewed according to the MHC criteria. RESULTS: There were 55 men and 53 women, with a median age of 34.5 years (range, 12 - 78 years). The interval between their first visit and clinical diagnosis was 3 days (range, 0 - 14 days). The diagnosis was made at the first visit in 7 (6.5%, 7/108) cases with a history of exposure to SARS patients and infiltrates on chest radiograph. Eighty-nine (82.4%) and 12 (11.1%) patients were categorized as probable cases and suspected cases respectively at their first visit and a clinical diagnosis of SARS was made subsequently. The interval between first visit and reaching the final diagnosis was 1 - 3 days in 72 (66.7%) cases and 4 days in 29 (26.9%) cases. The final diagnosis was made in 0 - 14 days (median, 2 days) for those (n = 59, 54.6%) with a history of close contact with SARS patients and 2 - 8 days (median, 3 days) for those (n = 49, 45.4%) living in Beijing but without such a history (P = 0.03). The chest radiograph was interpreted as unremarkable in 26 (24.1%) cases at their first visit, and the diagnosis was made in 4 days (range 2 - 8 days), which was significantly longer compared with other cases (P < 0.001). In patients without a history of close contact with SARS patients, all the five criteria were met after combination antibiotic therapy had failed. CONCLUSIONS: A chest radiograph without infiltrates at the early stage of SARS is an important factor responsible for delayed diagnosis. In patients without a history of close contact with SARS cases, antibiotic effect was a major factor influencing doctors' diagnosis.

[The levels and clinical implications of induced sputum interleukin-17 in chronic obstructive pulmonary disease and asthma].

OBJECTIVE: The study aims to investigate the changes of interleukin (IL)-17 in induced sputum, and to observe the correlation between concentrations of IL-17 and the number of inflammatory cells in induced sputum in chronic obstructive pulmonary disease (COPD) and in asthma. METHODS: Induced sputum was obtained in patients with COPD both during acute exacerbation and stable stage and in asthma during acute attack. Healthy nonsmoking volunteers were included as controls. The concentrations of IL-17 in induced sputum were measured by enzyme-linked immunosorbent assay. RESULTS: The concentrations of IL-17 both in patients with COPD during acute exacerbation and with asthma were significantly higher than that in the control subjects (P < 0.001). The levels of IL-17 in patients with COPD during acute exacerbation positively correlated with that of IL-8 (r = 0.381, P = 0.038) and with the percentage of neutrophils (r = 0.446, P = 0.010) respectively. There was also a positive correlation between the concentrations of IL-17 and the numbers of eosinophils in patients with asthma. CONCLUSION: The concentrations of IL-17 in patients with acute exacerbation of COPD and in patients with asthma were significantly increased. IL-17 may play a role in the airway inflammation in both COPD and asthma.

[The relationship between chronic obstructive pulmonary disease and Chlamydiae pneumoniae infection].

OBJECTIVE: To determine the possible association between Chlamydiae pneumoniae (Cpn) infection and chronic obstructive pulmonary disease (COPD). METHODS: This work comprised of two studies. The first was an animal study which involved 40 male Wistar rats. The animals were divided into 4 groups, 10 rats in each group. They were treated with cigarette smoking alone (group A), cigarette smoking and Cpn inoculation (group B), and Cpn inoculation alone (group C), respectively, with a group D as the control. After 6 weeks, Cpn DNA in the lung tissue was detected by PCR, and pulmonary function of the animals was measured. Lung pathological characteristics were scored. In the second study we used PCR to detect Cpn DNA in lung tissues from patients with COPD and control group, meanwhile Cpn IgG and IgA antibodies were also measured. RESULTS: The animal model of COPD was successfully replicated in most rats of group A (88.9%) and all of group B (100%). Group A was greater than group B in changes of pulmonary function, and higher in pulmonary pathological scores, predominantly in inflammatory cell infiltration and proliferation of small airway smooth muscle. There were no statistical differences between group C and group D in changes of pulmonary function. Pulmonary pathological scores were higher in group C than in group D, with statistical value, also predominantly in inflammatory cell infiltration and proliferation of small airway smooth muscle. The positive incidence of Cpn PCR were 88.9% and 80.0% in group A and C respectively. The positive rate of IgG and IgA were 82.4% and 58.8%, respectively. All pulmonary biopsy specimens of COPD and control group were negative. CONCLUSIONS: There were no direct relationship between COPD with Cpn infection. Infection with Cpn cannot induce COPD simply. But it can exacerbated the air obstruction of COPD on the bases of pulmonary impairment by cigarette smoking.

[Multicenter clinical trial on the efficacy of thrombolytic therapy with urokinase and/or anticoagulant with low molecular weight heparin in acute pulmonary embolism].

OBJECTIVE: To evaluate the efficacy of thrombolytic therapy with urokinase and/or anticoagulant with low molecular weight heparin in patients with acute pulmonary embolism. METHODS: 127 patients with documented acute pulmonary embolism were treated with different regimens: thrombolysis combined with anticoagulant therapy in 70 cases, thrombolytic therapy alone in 31 cases and pure anticoagulant therapy in 26 cases. RESULTS: Dyspnea was the most common symptom (91.3%), then cough (74.0%), chest pain (63.0%) and syncope (21.3%). As compared with pre-treatment in each group, there was significant improvement in respiratory rate, heart rate, partial pressure of oxygen in artery and partial pressure of carbon dioxide in artery. The effective rate of thrombolysis combined with anticoagulant therapy, thrombolytic therapy and anticoagulant therapy were 90.0%, 77.4% and 61.5%, respectively, the total effective rate of thrombolytic therapy was 86.1%. The best efficacy was demonstrated in patients within one week after onset of symptoms. The therapy might be effective for cases with duration longer than two weeks after the onset of symptoms. CONCLUSION: Thrombolytic therapy with urokinase combined with low molecular weight heparin is effective and safe for acute pulmonary embolism.

[Retrospective analysis for first-visiting case data of 272 SARS inpatients in Peking University Third Hospital].

OBJECTIVE: The first-visiting cases of total 272 SARS inpatients admitted in SARS wards in Third Hospital from April 10, 2003 to May 12 were analyzed retrospectively. The clinical characteristics and diagnostic decision for these patients were described. METHODS: The enrollment of inpatients was ruled with two official standards, i.e., 'Clinical Standards for Diagnosis of SARS, Trial Edition' from Health Ministry, and 'Diagnostic Standards for SARS' from Joint Force of Prevention and Therapy for SARS in Beijing, PRC. The present work was based on the first-visiting case records of these SARS inpatients. RESULTS: The characteristics of gender, age, occupation, contagious history and previous therapy were described in SARS inpatients when they visited the outpatient department for SARS in the first time; the clinical symptoms, physical signs, blood WBC counts and X-ray in lungs were also analyzed. In 272 inpatients who were admitted into SARS wards at their first visiting, 145 patients (53.5%) were finally diagnosed as SARS, well as 97 patients (35.7%) were eliminated. CONCLUSION: In the first visiting of the suspectable SARS patients, the contagious history, clinical symptoms, laboratory results and lung X-ray should be studied comprehensively and thoroughly to avoid omitted or mistaken diagnosis. Most final diagnosis came from the revising of the original decision. The advances in SARS virology and immunology may provide more accurate evidences in SARS diagnosis.

[Chest X-ray changes after discontinuation of glucocorticosteroids treatment on severe acute respiratory syndrome (5 cases report)].

OBJECTIVE: To investigate the effect of glucocorticosteroids on severe acute respiratory syndrome (SARS) and chest X ray changes after discontinuation of glucocorticosteroids treatment. METHODS: To retrospectively study the clinical characteristics of 5 cases with SARS and chest X ray changes after discontinuation of glucocorticosteroids. RESULTS: 5 cases were medical workers and had exposure to SARS patients. The incubation periods were 2 to 7 days. They had high fever from the onset of the disease. There were lung infiltrates 1 to 6 days after fever and then methylprednisolone was given to them. Two or three days after glucocorticosteroids treatment, clinical symptoms in these patients were disappeared. The clinical symptoms in case 1, cases 2, case 4 and case 5 weren't deteriorated after discontinuation of methylprednisolone while the presentation in chest X ray was progressed 3-6 days later. No more methylprednisolone was given to the patients and the infiltrates in chest X ray was gradually absorbed in 5-11 days. The temperature in case 3 was elevated again and the shadow in chest X ray was progressed after discontinuation of methylprednisolone due to the low dosage of glucocorticosteroids. When the dosage of methylprednisolone was increased, the temperature tended to be normal and the lung infiltrates began to absorb gradually. CONCLUSION: For the patients with non-severe SARS, if the symptoms were disappeared after discontinuation of glucocorticosteroids, the lung shadow may be progressed. we can closely observe the condition of the disease and no more glucocortisteroids needed to be given to the patients. The lung shadow could be absorbed gradually.