Biomedical subjects
Publications and source records attributed to Aixia Wang.
[reaction: see text] A practical and efficient total synthesis of (+/-)-galanthamine was achieved from commercially available materials through a novel approach, in which the construction of its core structure and the special allylic alcohol group were based on a successive semipinacol rearrangement/desilyation/cyclization and Saegusa-Ito oxidation, respectively.
BACKGROUND: It still remains controversial which kind of relationships exist between HIV-1-specific CD8 T-cell responses and HIV RNA load or CD4 count over the course of the infection. This study was designed to investigate the role of HIV-specific CD8 responses in patients with different disease status. METHODS: Three cohorts of patients were selected according to CD4 count levels: long-term nonprogressors (LTNPs, n = 19), asymptomatic progressors (CD4 counts between 500 and 350 cells/mm(3), n = 14), and progressors (CD4 counts <350 cells/mm(3), n = 23). Six of the LTNPs experiencing a quick loss of CD4 T-cells and another 6 LTNPs with stable CD4 counts were followed up. T-cell responses were studied using interferon (IFN) gamma-ELISpot assay against HIV p24 and 11 pools of HIV-Gag peptides. RESULTS: No significant differences were found in Gag-specific CD8 responses among the 3 cohorts. However, inverse correlations were identified between CD8 responses and CD4 counts in asymptomatic progressors and between CD4 responses and viral loads in progressors. In addition, the sequential dynamics of CD8 responses in 6 LTNPs showed that with a quick loss of CD4 T-cells around the range of 500 to 300 cells/mm(3), more vigorous CD8 responses were induced simultaneously, and plasma viremia was still kept relatively stable. CONCLUSIONS: These data suggest that the relationship between CD8 response and viral load or CD4 count is not universally consistent throughout the entire course of HIV-1 infection. Gag-specific CD8 responses may play differential roles in different stages of HIV-1 infection, and the maintenance of a threshold level of CD4 T-cells may contribute to mediate effective HIV-specific responses in natural control of HIV-1 infection.
A chelating resin coupling Amberlite XAD-2 functionalized with dithizone is synthesized and characterized. Dissolved cadmium is field-preconcentrated using a minicolumn packed with the synthesized resin and determined by flame atomic absorption spectrometry. Five experimental variables are evaluated. The enrichment factor of 416 is obtained for 50 mL of sampling volume, and the detection limit (3 sigma) of the procedure is 6.7 ng L(-1). The precision (RSD) for 11 independent determinations is 1.97%. This method has been successfully applied to the determination of cadmium in natural seawater samples.
Itraconazole has a broad spectrum of activity against the most common fungal pathogens. Prior problems with absorption in severely ill patients have been overcome with the introduction of an oral solution and an intravenous preparation. An open-labeled, non-competitive, multicenter phase IV study was conducted to investigate the efficacy and safety of itraconazole administered intravenously for the treatment of invasive fungal infections in Chinese patients. Patients were treated with itraconazole intravenously for 2 weeks (200 mg twice daily for 2 days, then 200 mg once daily for 12 days) followed by 28 days of oral capsules (200 mg twice daily). Efficacy evaluation included an assessment of the clinical efficacy, fungal efficacy and total efficacy on days 14 and 42. Of 156 evaluable patients, 35 patients had proven and 62 suspected invasive fungal infections, and 59 patients were treated empirically. On day 14 the total efficacy rate in patients with proven infection was 54.3% (19/35; 95% confidence interval [CI], 37-71%) and on day 42 it was 65.7% (23/35; 95% CI, 48-81%). The most common adverse events were hypokalemia (13.5%), gastrointestinal disorders (12.8%), elevation of liver enzymes (10.9%) and increase of bilirubin (8.3%). Itraconazole intravenously followed by oral capsules is thus tolerated and effective in severely ill patients with proven invasive fungal infection.
CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.
A general and efficient approach to both 7-aryloctahydroindole and cis-3a-aryloctahydroindole alkaloids has been developed. The key step involves Michael additions of the corresponding kinetics and thermodynamics lithium enolates of ketone 9 to the versatile building blocks: nitroethylene 10. Two representative members, (+/-)-gamma-lycorane and (+/-)-crinane, have been synthesized in 22 and 36% overall yields, respectively.
This report demonstrates that a rapid decrease of peripheral T cell subsets is a unique characteristic in patients with SARS during acute infection, although total white blood cell counts, red blood cell counts, and platelet counts remain relatively normal. In recovering patients, a rapid and dramatic restoration of peripheral T cell subsets was seen in the periphery. Although the underlying mechanism of the acute decrease of peripheral T cell subsets observed in patients with SARS during the acute stage remains unknown, this clinical characteristic can facilitate an earlier and more accurate diagnosis of SARS.
p120-catenin exists in a membrane-associated cadherin-bound pool, a cytosolic pool that affects Rho GTPases, and a nuclear pool that is thought to associate with the methylation-relevant transcriptional repressor Kaiso. We show here that cytoplasmic p120 can also associate both directly and indirectly with the microtubule network, and that p120 traffics along microtubules toward their plus ends. The direct binding required most of the armadillo repeats and was mutually exclusive for interaction with E-cadherin. Perturbing the p120-microtubule interaction with nocodazole or taxol markedly affected both the tubulin interaction and the balance between cytoplasmic and nuclear p120. The indirect binding occurred via a novel interaction between a segment of the p120 N-terminal domain and conventional kinesin heavy chains. Selective uncoupling of the p120-kinesin interaction by overexpression of the respective p120 and kinesin-binding fragments promoted nuclear p120 accumulation. In addition, expression of full-length kinesin reduced the nuclear accumulation of p120 and blocked the branching phenotype associated with p120 overexpression. Taken together, the data suggest that kinesin affects both the targeting and activity of p120 at several cellular locations.
OBJECTIVE: To study the alteration of peripheral lymphocyte subsets in severe acute respiratory syndrome (SARS) patients and to help improve the early diagnosis of the disease. METHODS: Anti-coagulating blood samples from 98 SARS patients in the acute phase, 56 normal healthy blood donors, and from patients infected by HIV, CMV and EBV were collected. The T lymphocyte subsets were counted by flow cytometry using fluorescence-labeled specific monoclonal antibodies. RESULTS: A significant decrease was observed in all SARS patients in their peripheral CD4(+) and CD8(+) T lymphocyte absolute counts [256 (104) x 10(6)/L and 256 (117) x 10(6)/L, respectively], which were also lower than those of the patients infected with HIV, CMV and EBV. All patients infected with HIV, CMV and EBV had significantly higher CD8(+) T lymphocyte counts in comparison with normal controls. CONCLUSIONS: Decrease of both CD4(+) and CD8(+) T lymphocytes of patients is related to onset of SARS. T lymphocyte subset analysis would help improve the early diagnosis of the disease.
OBJECTIVE: To study the T-lymphocyte immune alterations and its clinical significance in HIV-infected persons and AIDS patients in China. METHODS: Peripheral blood samples were collected from 13 HIV-infected persons, 27 AIDS patients, and 51 healthy blood donors (controls) and then labeled with monoclonal antibodies. Flow cytometry was used to detect the count of CD4(+) T-lymphocytes, CD8(+) T-lymphocytes, and its different subsets including the naive cell subset (CD4(+) CD45RA(+) CD62L(+)), activated cell subsets (CD4(+) HLA-DR(+), CD8(+) HLA-DR(+), CD8(+) CD38(+)), functional cell subsets (CD4(+) CD28(+)), and apoptotic cell subsets (CD4(+) CD95(+), CD8(+) CD95(+)). The plasma HIV loading was also detected. RESULTS: The CD4(+) cell count was (849 +/- 288) x 10(6)/L in the control group, significantly higher than that in HIV-infected person group [(437 +/- 184) x 10(6)/L, P < 0.01], and that in AIDS patient group [(50 +/- 51) x 10(6)/L, P < 0.01]. The CD8(+) cell count was (579 +/- 175) x 10(6)/L in the control group, significantly lower than that in HIV-infected person group [(1 031 +/- 345) x 10(6)/L, P < 0.05], and not significantly different from that in AIDS patient group (535 +/- 338) x 10(6)/L, with a significant difference between the HIV-infected person group and AIDS patient group (P < 0.05). The percentage of CD4(+) CD45RA(+) CD62L(+) were 43.0% +/- 11.4% in the control group, not significantly different from that in HIV-infected person group (44.2% +/- 12.8%), but significantly higher than that in AIDS patient group (24.8% +/- 15.5%, P < 0.05). The CD4(+) CD45RA(+) CD62L(+) cell count was (368 +/- 162) x 10(6)/L in the control group, significantly higher than those in HIV-infected person group [(185 +/- 134) x 10(6)/L] and in AIDS patient group [(18 +/- 20) x 10(6)/L, both P < 0.01] with a significant difference between the HIV-infected person group and AIDS patient group (P < 0.01). The percentage of CD4(+) CD28(+) was 93.1% +/- 8.1% in the control group, significantly higher than those in HIV-infected person group (62.6% +/- 28.2%) and in AIDS patient group (56.9% +/- 26.4%) with a significant difference between any two groups (all P < 0.01). The percentages of CD4(+) HLA-DR(+), CD8(+) HLA-DR(+), and CD8(+) CD38(+) in the AIDS patient group were higher than those in the HIV-infected person group and control group with significant difference between any two groups (all P < 0.01). The percentages of CD4(+) CD95(+) and CD8(+) CD95(+) in the AIDS patient group were not significantly different from that in control group, but significantly higher than that in HIV-infected person group (P < 0.05). The plasma HIV loading was 3.74 +/- 0.78 lg copies/ml in the HIV-infected person group and was 4.94 +/- 0.68 lg copies/ml in AIDS patient group (P < 0.05), and the count of CD4(+) cells and CD4(+) CD45RA(+) CD62L(+) cells were obviously negatively correlated with the plasma HIV loading (r = -0.796, r = -0.750, P < 0.01). CONCLUSION: The T-lymphocyte immune dysfunction occurring in HIV-infected persons and AIDS patients in China involves not only the number, but also the function and activation of T-lymphocytes. Synthetical analysis of the alterations of different T cell subsets reflects the immune deficiency and severity of disease more comprehensively than pure examination of the amounts of CD4(+) and CD8(+) cells.
OBJECTIVES: To evaluate the diagnostic value of PCR for detection of Pneumocystis carinii DNA from induced sputum samples. METHODS: P. carinii cysts or trophozoites were detected in induced sputa by Giemsa stain or Gomori Methenamine silver (GMS) stain. A fragment of the Pneumocystis carinii mitochondrial large-subunit rRNA gene was amplified from sputum samples using a one-step PCR method with mt-rRNA primers. RESULTS: In this study, sputum samples from 16 patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) and 20 patients with other respiratory infections were first tested by cytochemical staining. Pneumocystis carinii was detected in 8 and 0 sputum samples from the two groups, respectively. The sensitivity and specificity of cytochemical stain were 50% and 100%. With the one-step mt-rRNA-PCR method, Pneumocystis carinii DNA was detected in 14 and 0 sputum samples from 16 PCP patients and 20 non-PCP patients. The sensitivity and specificity of mt-rRNA-PCR was 88% and 100%, respectively. CONCLUSIONS: The specificity of both Giemsa and GMS staining of induced sputum samples is high and the methods are simple, but the sensitivity is low. The sensitivity of PCR for P. carinii DNA from induced sputum samples is significantly higher than cytochemical stains, and the method is highly specific when used in the clinical diagnosis of PCP.
OBJECTIVE: To study the diagnosis and therapy of cryptococcal meningitis. METHODS: Retrospective review of the clinical features, treatment and outcome of 26 patients with cryptococcal meningitis from October 1981 to September 2001 at Peking Union Medical College Hospital. RESULTS: The age of the patients ranged from 5 to 62 years (mean: 35.6 years), 12 were male and 14 were female. There were 16 patients with underlying diseases, 9 had systemic lupus erythematosus (SLE), 4 had human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome (AIDS) and 3 had other diseases. 12 patients had contact with pigeons. The nonspecific clinical and laboratory findings in these patients led to misdiagnosis: as lupus encephalopathy in 6 cases and tuberculous meningitis in 5 cases. 23 of the 26 cases were positive of cryptococcus on cerebrospinal fluid (CSF) smear. 13 cases were positive on CSF culture, but latex coagulate test performed in 20 cases were all positive, 15 patients had high intracranial pressure (> 300 mm H(2)O), 9 patients with dilated ventricle received brain ventricular draining. Only 2 cases used fluconazole monotherapy. One patient only used amphotericin B. The rest of the patients were given amphotericin B in combination with flucytosine (12 patients) or fluconazole (5 cases), or flucytosine combined with fluconazole (6 cases). The mean dose of amphotericin B was 2.6 g, the highest dose of amphotericin B and liposomal amphotericin B was 10.05 g and 20 g, respectively. The outcome of the 26 cases showed that 17 were cured, 4 improved, 3 patients were died and 2 patients gave up any further treatment. From Oct. 1981 to Sep. 1996 we found only 9 cases, but in recent 5 years we found 17 cases. CONCLUSIONS: The incidence of cryptococcal meningitis was increasing in the recent 5 years. The conditions associated with this disease include extensive broad spectrum antibiotics, immunosuppressive drugs or ligh-dose corticosteroids and increasing cases of HIV/AIDS. The early diagnosis and treatment of cryptococcal meningitis may reduce death rate. We still recommended amphotericin B plus flucytosine as the standard therapy for cryptococcal meningitis. Ventricular drainage and amphotericin B intraventricularly via an implanted tube into dilated ventricle could improve the clinical condition of serious cryptococcal meningitis and decrease the dosage of systemic use of amphotericin B, therefore, reduce the side-effects of the drugs.