Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway in jurkat cells.

Previous studies have suggested that microsomal prostaglandin E synthase-1 (mPGES-1) is highly expressed and closely associated with mitogen-activated protein kinase (MAPK) signaling pathways in various types of malignant cells. However, their expression patterns and function with respect to T-cell acute lymphoblastic leukemia (T-ALL) remain largely unknown. The present study investigated whether mPGES-1 served a crucial role in T-ALL and aimed to identify interactions between mPGES-1 and the MAPK signaling pathway in T-ALL. The results indicated that mPGES-1 overexpression in T-ALL jurkat cells was significantly decreased by RNA silencing. Decreasing mPGES-1 on a consistent basis may inhibit cell proliferation, induce apoptosis and arrest the cell cycle in T-ALL jurkat cells. Microarray and western blot analyses revealed that c-Jun N-terminal kinase served a role in the mPGES-1/prostaglandin E2/EP4/MAPK positive feedback loops. In addition, P38 and extracellular signal-regulated kinase 1/2 exhibited negative feedback effects on mPGES-1. In conclusion, the results suggested that cross-talk between mPGES-1 and the MAPK signaling pathway was very complex. Therefore, the combined regulation of mPGES-1 and the MAPK signaling pathway may be developed into a new candidate therapy for T-ALL in the future.

[Effects of shRNA Targeting mPGES-1 on Tumorigenicity of K562 Cells in Nude Mice In Vivo].

OBJECTIVE: To investigate the effects of shRNA targeting mPGES-1 on tumorigenicity of human acute leukemia K562 cells in nude mice in vivo and its mechanisms. METHODS: For experiment 3 groups including KD group(expression of mPGES-1 in K562 cells was down-regulated by shRNA), CON (cells without any treatment) and NC group (cells treated with nonspecific-sequence shRNA) were set-up. Western blot was used to test the expression of ß-catenin and cyclinD1 in cells. Then the cells of 3 groups were implanted into BALB/c nude mice subcutaneously to establish murine xenograft model. The growth state of the mice and the size of the xenograft tumor were recorded. HE staining was used to observe the morphology of xenograft tumor. Expressions of ß-catenin and cyclinD1 in xenograft tumor were detected by immunohistochemical staining. RESULTS: In vitro the expression of ß-catenin and cyclinD1 in KD group were lower than the CON group and NC group (P<0.05). In vivo the tumor volume and weight of KD group were significant smaller than the other two groups (P<0.01). HE staining showed that tissues in the KD group were relatively looser in arrangement with smaller cell nucleus and less cytoplasm. The expression of ß-catenin and cyclinD1 in the KD group were remarkable weak as compared with that in CON group and NC group (P<0.05). CONCLUSION: Down-regulating the expression of mPGES-1 by shRNA may significantly inhibit the tumorigenicity of K562 cells in nude mice in vivo and its mechanism may be related with the inhibition of expression of ß-catenin and cyclinD1.

[Protective effects of human bone marrow mesenchymal stem cells on hematopoietic organs of irradiated mice].

The objective of this study was to explore the protective effects of human bone marrow mesenchymal stem cells (MSC) on hematopoietic organs of irradiated mice. Human bone marrow MSC were isolated, ex vivo expanded, and identified by cell biological tests. Female BALB/c mice were irradiated with (60)Co γ-ray at a single dose of 6 Gy, and received different doses of human MSC and MSC lysates or saline via tail veins. The survival of mice was record daily, and the femurs and spleens were harvested on day 9 and 16 for pathologic examination. The histological changes were observed and the cellularity was scored. The results showed that the estimated survival time of MSC- and MSC lysate-treated mice was comparable to that of controls. The hematopoiesis in the bone marrow of mice that received high-dose (5×10(6)) of MSC or MSC lysates was partially restored on day 9 and the capacity of hemopoietic tissue and cellularity scorings were significantly elevated as compared with that of controls (P < 0.05). Proliferative nudes were also obviously observed in the spleens of mice that received high-dose of MSC or MSC lysates on d 9 after irradiation. The histological structures of the spleen and bone marrow of the mice that received high-doses (5×10(6)) of MSC or MSC lysates were restored to normal, the cell proliferation displayed extraordinarily active. Further, the cellularity scores of the bone marrow were not significantly different between the high-dose MSC and MSC lysate-treated mice. It is concluded that the bone marrow MSC can promote the hematopoietic recovery of the irradiated mice, which probably is associated with the bioactive materials inherently existed in bone marrow cells.

[Effect of human bone marrow mesenchymal stem cell transplantation on hematopoietic recovery of irradiated mice].

This study was aimed to investigate the effect of human bone marrow mesenchymal stem cells (hBMMSC) on the hematopoietic recovery of sublethally irradiated mice. Female BALb/c mice irradiated with (60)Co γ-ray at a single dose of 6 Gy received graded doses of hBMMSC (1×10(5), 1×10(6) and 5×10(6)) by intravenous infusion. The counts of leukocytes, platelets, erythrocytes and hemoglobin level in peripheral blood, the amount of bone marrow hematopoietic progenitors, and the serum levels of human TPO, SCF and G-CSF as well were evaluated at different time points after transplantation. The results showed that hBMMSC infusion had little protective effect on the survival of irradiated mice. Compared with the control mice, the peripheral blood cell counts of hBMMSC-treated mice were not obviously elevated during 3 weeks after infusion, however, blood cell counts were significantly greater at 4 weeks after cell treatment (P < 0.05). The amount of colony-forming unit of mononuclear cells and granulocyte/monocytes in bone marrow of mice that received middle and high doses of hBMMSC were dramatically greater than that in control mice (P < 0.05). Two days after hBMMSC administration, human G-CSF and SCF could be detected in the sera from hBMMSC-treated mice, and the G-CSF concentration of mice that received high-dose hBMMSC was significantly higher than that in other groups (P < 0.01). Nevertheless, human TPO was undetectable in the sera of all mice tested and serum human G-CSF and SCF could not be detected on days 9 and 16 in all groups. It is concluded that hBMMSC may promote the hematopoietic recovery of irradiated mice, probably by transient secretion of hematopoiesis-associated factors by the implanted cells.

[Effect of mPGES-1 inhibitor MK886 on cell cycle of leukemia HL-60 cells].

To investigate the effect of a microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor MK886 on cell cycle of the human acute myeloid leukemia HL-60 cells. HL-60 cells were treated with different concentration of MK886 (10, 25, 50 µmol/L) for 24 h. Flow cytometry, Western blot and ELISA were used to measure cell cycle, cyclin D1, mPGES-1, PGE(2), Akt, P-Akt and C-MYC. The results indicated that after treated with MK886, the percentage of HL-60 cells decreased in G(0)/G(1) phase and increased in S phase, and expressions of mPGES-1, cyclin D1, P-Akt and C-MYC and synthesis of PGE(2) decreased significantly. It is concluded that MK886 can arrest HL-60 cells in G(0)/G(1) phase, the mechanism of which is possibly associated to inhibition of mPGES-1 expression, reduction of PGE(2) synthesis, suppression of Akt phosphorylation and C-MYC expression, down-regulation of cyclin D1 expression.

[Effect of mPGES-1 inhibitor MK886 on apoptosis and drug resistance of HL-60/A cells].

This study was aimed to investigate the effect of MK886, a mPGES-1 inhibitor, on apoptosis and drug resistance of leukemia HL-60/A cell line. Expression of mPGES-1 was assayed by QT-PCR and Western blot. The effect of MK886 on HL-60/A cell proliferation was assayed by CCK-8 method, and flow cytometry was used to detect cell apoptosis. The expression of Akt and P-Akt was detected by Western blot. PGE2 was measured by ELISA. Effect of MK886 (10 µmol/L) on the chemotherapeutic sensitivity of HL-60/A cells and expression of mdr-1 mRNA and P170 protein were investigated too. The results indicated the expression of mPGES-1 was higher in HL-60/A cells. MK886 inhibited HL-60/A cell proliferation and induced apoptosis in a time- and concentration-dependent manner. Expression of mPGES-1 and P-Akt and synthesis of PGE2 decreased significantly. MK886 reduced expression of mdr-1 and P170 protein and enhanced the sensitivity of HL-60/A cells to chemotherapeutic drugs. It is concluded that MK886 can inhibit HL-60/A cell proliferation, induce apoptosis and enhance sensitivity to chemotherapeutic drugs, the mechanism of which possibly associates to down-regulation of mPGES-1/PGE2 synthesis, reduction P-Akt expression and decreasing mdr-1 and P170 protein expression.

[Cyclin D1, hTERT expression and telomerase activity in HL-60 and HL-60A cell lines and their significance].

To observe the expression of cyclin D1, hTERT, and telomerase activity in MNC, HL-60, HL-60A and to explore their effects on leukemogenesis and drug-resistance, normal human peripheral blood mononuclear cells, HL-60 cells sensitive to adriamycin and HL-60A cells resistant to adriamycin were investigated. The cell cycle was analyzed by flow cytometry, and the apoptosis was analyzed by Annexin V-FITC(+) PI staining. Expressions of cyclin D1 and hTERT were determined by real-time PCR and Western blot. Telomerase activity was detected by TRAP-ELISA. The results indicated that the percentage of MNC, HL-60 and HL-60A in S phase was (10.21 + 2.11)%, (44.93 + 3.00)%, and (51.38 + 1.10)% respectively; the percentage of apoptosis cells was (16.14 + 2.13)%, (7.53 + 0.92)%, (4.15 + 0.96)% respectively; the expression of mRNA and protein for cyclin D1 and hTERT increased; the telomerase activities of HL-60 and HL-60A were higher (p = 0.000), whereas the difference between HL-60 and HL-60A was no statistically significant (p = 0.232); positive correlation between cyclin D1, hTERT and telomerase activity had been found (p < 0.01). It is concluded that the cells of S phase increased while the apoptotic cells decreased in HL-60 and HL-60A, especially in HL-60A, which may be due to the up-regulation of cyclin D1, hTERT and telomerase activity.

[Effect of valproic acid on apoptosis of leukemia HL-60 cells and expression of h-tert gene].

This study was aimed to clarify whether valproic acid (VPA) induces apoptosis of leukemia HL-60 cell line and its possible mechanism. The effect of different concentrations and treatment time of VPA on HL-60 cell proliferation was assayed by cytotoxicity test (CCK-8 method) and fluorescence microscopy, and flow cytometry was used to detect cell apoptosis. The expressions of telomerase subunit h-tert mRNA and apoptosis-related protein as well as caspase-3 activity were detected by real time-quantitative PCR, Western blot and ELISA respectively. The results indicated that VPA inhibited proliferation of HL-60 cells and induced cell apoptosis in a dose dependent manner (r = -0.87). The expressions of anti-apoptotic protein BCL-2 and h-tert mRNA were significantly decreased while the pro-apoptotic protein BAX and caspase-3 activity increased after treatment with VPA. The apoptosis rate of HL-60 cell was negatively correlated with expression of h-tert mRNA. It is concluded that VPA can inhibit leukemia HL-60 cell proliferation and induce apoptosis. The VPA displays anti-leukemia activity possibly through reducing h-tert mRNA and BCL-2 protein expression, increasing BAX expression and activity of caspase-3.

[Immuno-regulatory effect of 3'-meisoindigo in mice of various germlines].

OBJECTIVE: To investigate the effect of 3'-meisoindigo on the proliferation and the biological function of the splenocyte and thymocyte of mouse, which were 8 weeks old masculinity BALB/c, C57BL/6 and F1 hybridization mouse. METHODS: Cells of thymus and spleen were harvested and prepared as the unicell suspension, then treated with 5, 10, 15, 20, 25 micromol/L 3'-meisoindigo. The cell proliferation was by MTT method, concentration of IL-12 was dectected by ELISA method, the mRNA levels of Bcl-2 and CDK2 were decected by RT-PCR. The cell cycle, apoptosis ratio, death ratio and intracellular ROS concentration were detected by FCM method. The protein level of Bcl-2, CDK2 and Bax were detected by immumofluorescence method. RESULTS: 15, 20, 25 micromol/L 3'-meisoindigo can inhibit the proliferation of thymocyte and splenocyte (P < 0.05). It had dose-dependent and time-dependent manner. 3'-meisoindigo inhibit the secretion of IL-12, even at 5 micromol/L concentration. 15 micromol/L 3'-meisoindigo decrease the mRNA level of Bcl-2 and CDK2, induced apoptosis and G2 arrestting of the thymocyte and splenocyte. (P < 0.05). The intracellular ROS level increased after treated by 3'-meisoindigo at 15 micromol/L for 24 h (P < 0.05). There were no difference among three germ line mouse. CONCLUSION: Above 15 micromol/L, 3'-meisoindigo can inhibit the proliferation and externalization function of thymocyte and splenocyte from different germ line mouse, meanwhile the mRNA and protein level of Bcl-2 and CDK2 decrease, the Bax protein expressed increased, the intracellular ROS level increase too.

[Effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of HL-60/HT cells].

OBJECTIVE: To investigate the effect of valproic acid on the expression of P27(Kip1) and P170 and drug resistance of leukemia HL60/HT cell line and explore its possible mechanisms. METHODS: HL-60/HT cells were derived from HL-60 cells induced by harringtonine (HT) in gradient concentrations. The inhibitory effect of valproic acid on the proliferation of HL-60 and HL-60/HT cells was evaluated by MTT assay, and the P27(Kip1) expression, P170 expression and cell cycle of the cells were analyzed with flow cytometry. RESULTS: The multidrug-resistant HL-60/HT was acquired, which showed a stable drug-resistant index with increased IC(50) of HT, VCR, DNR and Ara-c by 9.30, 5.20, 4.91 and 3.65 folds, respectively, as compared with those of HL60 cells. The expression of P27(Kip1) in HL-60/HT cells was significantly lower but P170 expression significantly higher than that of HL-60 cells and normal mononuclear cells (P<0.05). The expressions of P27(Kip1) and P170 showed no significant difference between normal mononuclear cells and HL-60 cells. The growth inhibition rate of VPA combined with Ara-C was significantly higher than that of valproic acid or Ara-C alone in HL-60/HT cells and HL-60 cells (q=1.37 and 1.51, respectively). HL-60/HT and HL-60 cells cultured in the presence of VPA resulted in a significant increase in the expression of P27(Kip1) and the G(1)-phase cells (P<0.05), but the expression of P170 underwent no significant changes (P>0.05). CONCLUSION: HL-60/HT cells have lower P27(Kip1) expression compared with HL-60 cells. Valproic acid can inhibit the growth of HL-60/HT cells and enhance their Ara-C sensitivity possibly by increasing P27(Kip1) expression and causing cell cycle arrest in G(1) phase.

[Experimental study on anti-platelet effects of ginsenoside -2A in vitro].

OBJECTIVE: To explore the in vitro anti-platelet effects of Ginsenoside -2A,a purified extract from Panax notoginseng. METHODS: Platelet rich plasma (PRP) was prepared routinely from venous blood samples of patients with essential hypertension and normal persons. PRP was incubated with different concentrations of Nifedipine, Ginsenoside-2A ,and SK&F96365. Maximal platelet aggregation rate[ PAG (M) ] induced by 2 micromol/L ADP was taken as the observed index. Five-minute PAG( M) was determined for 5 consecutive times. RESULTS: (1) PAG (M) in essential hypertension group was 0. 89 +/- 0. 06, which was higher than that in the normal group (0. 68 +/-0. 07 ) with significant difference (P <0.01). (2)Nifedipine of two concentrations (10 p.mol/L,20 pVmol/L) had no effect on PAG(M) in either essential hypertension group or normal group(P >0. 05). (3)Different concentrations of SK&F96365 (2.5 micromol/L,5 micromol/L,10 micromol/L and 20 micromol/L) could inhibit the PAG(M) in essential hypertension group; (4) Differen concentrations of Ginsenoside -2A (2. 5 micromol/L, 5 micromol/L, 10 micromol/L and 20 micromol/L) could inhibit PAG ( M) in essential hypertension group; three concentrations of Ginsenoside -2A (5 micromol/L, 10 micromol/L, 20 micromol/L) could inhibit the PAG(M) in the normal group (all P <0.05). CONCLUSION: Platelet aggregating function in essential hypertension patients was obviously higher than that in the normal persons and platelets was in the high reactive status. Nifedipine had no inhibitive effect on platelet aggregation. SK&F96365 could inhibit the platelet aggregation. Ginsenoside-2A could inhibit platelet aggregation, and had the definite anti-platelet action.

[The effects of chloride channel blockers on thrombocytic cytoplasmic free calcium concentration and platelet aggregation].

OBJECTIVE: To explore the effects of chloride channels on the regulation of platelet cytoplasmic free calcium concentration ([Ca2+]i) and platelet aggregation (PAG). METHODS: Freshly separated platelets were activated by thrombin. Chloride channel blockers DIDS or NFA and calcium channel blockers SK&F96365 or nifedipine were added to study the effects on platelet [Ca2+]i and PAG by a single reagent or the combination of reagents and find out the interactions among DIDS, NFA, SK&F96365 and nifedipine. RESULTS: Both DIDS and NFA could inhibit the thrombin (1 U/ml) induced PAG in a dose-dependent manner, whereas had little effect on resting [Ca2+]i. As compared with the control group, DIDS, SK&F96365 and Nifedipine could significantly reduce the PAG, Ca2+ release and Ca2+ influx in thrombin activated platelet (P < 0.05). The combination of DIDS and SK&F96365 had greater effects in reducing the PAG, Ca2+ release and Ca2+ influx than either reagent alone (P < 0.05). The combination of DIDS and nifedipine also had greater effect than each alone in reducing Ca2+ release (P < 0.05). The combination of NFA and SK&F96365 weakened each other's effect on Ca2+ release (P < 0.05), while NFA and nifedipine weakened each other's effects on PAG, Ca2+ release and Ca2+ influx in thrombin activated platelet (P < 0.05). CONCLUSION: DIDS and NFA have no effect on the resting [Ca2+]i and the leak calcium influx of platelet. DIDS can inhibit the Ca2+ release, Ca2+ influx and PAG of platelet induced by thrombin, while NFA can only inhibit the Ca2+ release. The chloride channel and calcium channel blockers have interactions in affecting resting [Ca2+]i and PAG of platelet. The opening of chloride channel can influence the cellular calcium movement of platelet.

[Study on the variation of platelet function in pregnancy induced hypertension and gestational diabetes mellitus].

OBJECTIVE: To investigate the platelet activity and function in pregnancy induced hypertension (PIH) and gestational diabetes mellitus (GDM). METHODS: Twenty-one patients with GDM and 23 patients with PIH in third-trimester were included. Twenty normal pregnant women in third-trimester served as controls. Platelet count (PC), mean platelet volume (MPV) were determined on Cell-DYN 1600 and the expression of CD62P was analyzed on FACSC alibur. RESULTS: (1) PC was (181 +/- 56) x 10(9)/L in PIH, (206 +/- 60) x 10(9)/L in GDM and (229 +/- 56) x 10(9)/L in controls, respectively. PC in PIH was lower than that of controls (P < 0.01), but there was no significant difference between GDM and controls. (2) MPV was (11.2 +/- 2.0) fl in PIH, significantly higher than that of controls (8.7 +/- 1.6) fl (P < 0.001). In GDM, MPV was (9.5 +/- 1.6) fl, without significant difference compared with that of controls. (3) The expression of CD62P increased significantly in PIH compared with controls [CD62P: (42 +/- 13)% vs (26 +/- 7)%, P < 0.001; CD62P(I): 109 +/- 39 vs 75 +/- 13, P < 0.01]. In GDM, the expression of CD62P also increased significantly compared with the normal pregnancy [CD62P(%): (42 +/- 14)% vs (26 +/- 7), P < 0.001; CD62P(I): 100 +/- 42 vs 75 +/- 13, P < 0.05]. (4) All parameters had no significant difference between PIH and GDM. CONCLUSION: Platelet activity is enhanced in PIH and GDM. It may play an important role in the pathogenesis and development of the two diseases.

[The effects of pravastatin on platelet-derived nitric oxide system in rabbits].

OBJECTIVE: To observe the effects of pravastatin on platelet-derived nitric oxide system in hypercholesterolemia (HC) and atherosclerosis (AS) in rabbits, and the relationship between these changes and atherosclerosis courses. METHODS: Thirty male New Zealand white rabbits were randomly divided into three groups, 12 in group A, 12 in group B, and 6 in group C. All of them were fed daily with cholesterol-rich food during the first 12 weeks. In addition, in group A, pravastatin (10 mg) was orally administered daily. At the end of the 12th week, 6 in group A and B were killed randomly and their aortas were removed and the pathologic changes were observed. In the following 12 weeks, food enriched with cholesterol was substituted with normal food in all three groups. Pravastatin treatment was continued or started in the remaining members of group A and group B, but not in group C. At the end 24th week, all rabbits were killed and their aortas were examined for the fatty-streaks or atherosclerotic plaques. The expressions of endothelial NOS (eNOS) mRNA and inducible NOS (iNOS ) mRNA, NOS activity, NO production and the level of the serum lipids were measured at 0, 6th, 12th, 18th and 24th week. RESULTS: The expression levels of platelet-derived NOS mRNA, eNOS mRNA ratio in group A had no difference at above time points, while in group B were reduced significantly at 6th week and 12th week compared with at 0 week (P <0.01), and increased at 18th week and 24th week compared with 12th week (P <0.05). The expression levels of eNOS mRNA in group C were reduced at 6th, 12th and 18th, 24th week compared with 0 week (P <0.05 and P <0.01, respectively), and were reduced in groups B and C compared with group A at 6th ,12th week (P < 0.05) and increased in group A and B compared with group C at 18th, 24th week (P <0.01). The expression levels of iNOS/mRNA among the three groups had no difference. Pathologic finding of the arteries: AS was not found in group A from the 12th to 24th week. While in group B, there were a lot of fatty-streaks on the entire intima of all large arteries at the 12th week. There were also fatty-streaks in the ascending aorta, but were improved at the 24th week. In group C, there were marked plaques in the entire aorta at the 24th week. CONCLUSIONS: The expressions of platelet-derived eNOS mRNA, NOS activity, NO production are decreased in HC or AS rabbits. Pravastatin can up-regulate expressions of platelet-derived eNOS mRNA, NOS activity, leading to preventing or improving the pathological courses of AS.

[Effects of 2A-1-1 on the aggregation and Ca2+ influx of platelets].

OBJECTIVE: To explore the effects of 2A-1-1 (purified component from Panax notoginsengs saponins) on the aggregation of and Ca2+ influx into human platelets. METHODS: The aggregation of platelets was tested by nephelometry, Fura-2 fluorescent technique was used for detecting cell [Ca2+]i. The effects of 2A-1-1, nifedipine and SK&F96365 on Ca(2+) influx into human platelets induced by ADP or CPA were observed separately. RESULTS: Nifedipine (< 20 micromol/L) could not inhibit platelet aggregation induced by ADP or the Ca(2+) influx induced by ADP or CPA. SK&F96365 at 20 micromol/L could inhibit the maximal aggregation of platelets induced by ADP with a inhibitory rate of 59.83%, at 15 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. 2A-1-1 (5, 10 and 20 micromol/L) could inhibit the maximal aggregation of platelets induced by ADP with the inhibitory rates of 47.06%, 53.47% and 71.52%, respectively. 2A-1-1 at 10 and 20 micromol/L could inhibit the Ca2+ influx induced by CPA or ADP. CONCLUSIONS: 2A-1-1 can inhibit platelets aggregation, block the ROC (Receptor-dependent Ca2+ channels) and inhibit Ca2+ influx of human platelets.

[Comparison of clinical features of severe acute respiratory syndrome among different transmission generations].

OBJECTIVE: To investigate the differences among various transmission generation of severe acute respiratory syndrome (SARS) by comparing the corresponding clinical data. METHODS: The clinical data of 84 patients with SARS were retrospectively studied, 66 women and 18 men, mean age (29.2 +/- 10.3) years old, 96.4% of whom were health care workers. All subjects had exposure to a source patient and the epidemic progressively propagated in a short time. For the infectious chain, we defined these patients who had exposure to a source patient as the primary cases, which included 35 patients (41.7%). Patients who got the disease by exposure to the primary cases were defined as secondary cases, which included 34 patients (40.5%). Similarly, the tertiary cases included 15 patients (17.9%). RESULTS: (1) No statistical differences in age, sex ratio, incubation period and hospitalization duration among various infectious generations were found (P > 0.05). (2) With descending in infectious generations, the initial temperature lowered, and cases with cough decreased (P < 0.05) with no statistical differences in the peak temperature, other accompanying symptoms and leukopenia (P > 0.05). (3) With descending in infectious generations, the course from the appearance of pulmonary lesions to their resolution shortened (P < 0.05). No differences were found in the maximal involved pulmonary fields, duration from initial fever to appearance of pulmonary lesions and course from the initial pulmonary lesions to their peak among the above three generations (P > 0.05). (4) No statistical differences were found in ways of oxygen therapy and classes of antibiotics prescribed (P > 0.05). With descending in infectious generation, cases treated with methylprednisolone, human gamma-immunoglobulin, interferon-alpha, and antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and the duration of their use also increased (P < 0.05). CONCLUSIONS: With descending in infectious generations, the clinical features of SARS may become ameliorated.

Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission.

BACKGROUND: Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS: The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS: There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS: There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.

[A study of the architectural factors and the infection rates of healthcare workers in isolation units for severe acute respiratory syndrome].

OBJECTIVE: To investigate measures to prevent the outbreak of severe acute respiratory syndrome (SARS) in healthcare workers in isolation units. METHODS: The architectural factors and the infection of healthcare workers in different wards in our hospital between 30 January 2003 and 30 March 2003 were analyzed. RESULTS: Four kinds of isolation wards were evaluated, including the ward where the thirty-first bed lied in on the twelfth floor, the laminar flow ward in the intensive care unit (ICU) where the tenth bed lied in on the fifteenth floor, the ward where the twenty-seventh bed lied in on the thirteenth floor of Building A, and thirty wards on the fourteenth to eighteenth floors of Building B. The ratios (m2/m3) of the area of the ventilation windows to the volume of the room were 0, 0, 1:95 and 1:40, respectively. Numbers of SARS cases in the wards mentioned above were 1, 1, 1 and 96, respectively. The total lengths (hour) of hospitalization were 43, 168, 110 and 1,272, respectively. The infection rates of the healthcare workers in the areas mentioned above were 73%, 32%, 28% and 2%, respectively. The difference of the infection rates was of statistical significance. CONCLUSION: In addition to strict personal protective measures, isolation of SARS cases in wards with high ratio of the area of ventilation windows to the volume of the room and good ventilation may be the key to preventing the outbreak of SARS in healthcare workers in isolation units.

[Research on physiological function of CD47].

CD47, also known as integrin-associated protein (IAP), is an ubiquitously expressed 50 kD cell membrane glycoprotein. This article reviews that as an integrin-associated molecule, CD47 regulates a series of integrin-dependent cell functions; CD47 regulates cell adhesiveness, migration and activation and platelet aggregation through binding to thrombospondins; CD7 is the extracellular ligand for human signal-regulatory proteins, thus it causes negative regulatory effect; CD47 induces costimulatory signals on activation of T cell, T cell apoptosis and T cell anergy and enhances the efficiency of TCR signaling; CD47 is a member of Rh antigen complex. CD47 is involved in stroma-supported erythropoiesis. This review also discussed that CD47 as a marker on red blood cells, associated with haemolysis, which provides a new way to recognize, diagnose, and treat diseases.