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Biomedical subjects

W Zou

Publications and source records attributed to W Zou.

At least 73 records · Page 4Linked to original sources

Synthesis and NMR assignment of two repeating units (decasaccharide) of the type III group B Streptococcus capsular polysaccharide and its 13C-labeled and N-propionyl substituted sialic acid analogues.

For the purpose of carrying out a comprehensive investigation into the nature of the conformational epitope of the type III group B Streptococcus polysaccharide, combined chemical and enzymatic methods were applied to the synthesis of three decasaccharide probes, namely beta-D-Glc-(1-->6)[alpha-NeuR-(2-->3)-beta-D-Gal-(1-->4)] -beta-D-GlcNAc-(1-->3)-beta-D-Gal-(1-->4)-beta-D- Glc-(1-->6)[alpha-NeuR-(2-->3)-beta-D-Gal-(1-->4)]-beta-D-GlcNAc-( 1-->3) -beta-D-Gal-OMe (22 NeuR = NeuAc; 23 NeuR = NeuAc with 8% 13C-labeling; 24 NeuR = NeuPr). The precursor core octasaccharide 21 was chemically synthesized from trisaccharide donor 11 and pentasaccharide acceptor 19 by block condensation. Sialylation of 21 with alpha-(2-->3)-sialyltransferase and CMP-NeuAc afforded 22. In the presence of CMP-sialic acid synthetase and alpha-(2-->3)-sialyltransferase, 21 was sialylated with sialic acid derivatives (8% 13C-labeled, or N-propionyl substituted) to give 23 and 24, respectively. Complete assignments of the 1H and 13C NMR spectra of compounds 21, 22 (23), and 24 are also presented.

Bacterial Capsules↗

Influenza infection in humans and pigs in southeastern China.

The three last pandemic strains of influenza A virus-Asian/57, Hong Kong/68 and Russian/77-are believed to have originated in China. The strains responsible for the 1957 and 1968 human pandemics were reassortants incorporating both human and avian influenza viruses, which may have arisen in pigs. We therefore undertook a population-based study in the Nanchang region of Central China to establish the prevalence, types and seasonal pattern of human influenza infection and to screen serum samples from animals and humans for evidence of interspecies transmission of influenza viruses. Two definite influenza seasons were demonstrated, one extending from November to March and the other July to September. The profile of antibodies to commonly circulating human influenza viruses was no different in Nanchang and neighboring rural communities than in Memphis, Tennessee, USA. In particular, Chinese women who raised pigs in their homes were no more likely to have been exposed to influenza virus than were subjects who seldom or never had contact with pigs. However, we did obtain evidence using isolated H7 protein in an enzyme-linked immunoabsorbent assay for infection of pig farmers by an avian H7 influenza virus suggesting that influenza. A viruses may have been transmitted directly from ducks to humans. The results of the serological survey also indicated that pigs in or near Nanchang were infected by human H1N1 and H3N2 influenza viruses, but not with typical swine viruses. We found no serological evidence for H2 influenza viruses in humans after 1968.

Adolescent↗

Morphological observations of vas deferens occlusion by the percutaneous injection of medical polyurethane.

Histological observations of 20 occluded vas segments obstructed by the standard procedure of medical polyurethane-vas occlusion in 10 volunteers requesting vasectomy and of 20 vas segments with plugs removed from 10 vas-occluded men requesting vas reversal were carried out in order to elucidate the mechanism of vas occlusion by medical polyurethane (MPU). Twenty vas deferens in vasectomy group were ruptured, only a small amount of MPU elastomer remained within the vas lumen, most having leaked through to encircle the ruptured vas. Histomorphology of the removed vas segments from 10 vas-occluded men, who had undergone MPU-vas occlusion 4 years earlier, showed diffuse proliferation of connective tissue, fibrosis, or hyalinization of fibroplastic tissue and local infiltration of lymphocytes and macrophages. The vas lumen both proximal and distal to the plugs was completely blocked. Sperm granuloma, foreign body granuloma, proliferation of nerve fibers and local infiltration of lymphocytes were found in four vas-occluded men with painful nodules. These results suggest that the contraceptive mechanism of MPU-vas occlusion could be the result of secondary obstruction due to tissue proliferation by MPU irritation after the rupture of the vas deferens.

China↗

[Immunotactoid glomerulopathy].

OBJECTIVE: To describe 3 patients with immunotactoid glomerulopathy (IT) and their clinicopathological features. METHODS: Renal biopsies were examined by EM: they were collected during the last 3 years in Department of Nephrology, First Hospital of Beijing Medical University. The amyloidosis, fibrillary glomerulopathy (FGP) and other systemic disease were excepted by clinical analysis, LM, IF, Congo red staining and image pattern analysis. RESULTS: The ultrastructural characteristic of the three cases were microtubular fibrils (diameter: 35-47 nm) deposited in various sites of glomeruli (GBM, subendothelium and mesangium) and electron dense deposits. In addition, randomly fibrillary deposits (diameter: 20 nm) were also found. The fibrils were negative with Congo red staining. The 3 patients were young middle-aged men with proteinuria, microscopic hematuria and hypertension, two of them had renal insufficiency. CONCLUSIONS: IT is a rare nephropathy but exists in China. Our, patients, were younger Than reported and there prognosis were poor. The microtubular and fibrillary deposits appear in some cases, indicating that IT and FGP are different subtypes of an entity.

Adult↗

[Interrelationship between endothelin and glomerular mesangial cells].

The interrelationship between endothelin (ET), endothelin receptors (ET-R) and glomerular mesangial cells (MC) was investigated by MC culture, RT-PCR, Northern blot hybridization, DNA cytometry and immunohistochemistry methods. The results showed that in MC, there existed the expression of ET mRNA and also the expression of 2 subsets ETA mRNA and ETB mRNA. ET mRNA peptide is synthesized in MC. ET mRNA induced significant MC contraction and stimulated MC division and proliferation. The results suggest that MC are special cells with the capacity of producing ET and are also the target cells for ET. It is possible that ET influence glomerular filtration area and rate by inducing MC contraction and cause also MC proliferation and glomerular sclerosis.

Animals↗

T helper type 1/T helper type 2 cytokines and T cell death: preventive effect of interleukin 12 on activation-induced and CD95 (FAS/APO-1)-mediated apoptosis of CD4+ T cells from human immunodeficiency virus-infected persons.

Human immunodeficiency virus (HIV) infection leads to a progressive loss of CD4+ T helper (Th) type 1 cell-mediated immunity that is associated with defective in vitro CD4+ T cell proliferation and abnormal T cell death by apoptosis in response to T cell receptor (TCR) stimulation. Quantification of interleukin (IL)-2, interferon gamma, IL-4, IL-5, and IL-10 secretion by immunoassays, and of interferon gamma, IL-4 and IL-10 messenger RNA expression by competitive reverse transcriptase polymerase chain reaction after in vitro stimulation of the TCR revealed a similar Th1 cytokine profile in T cells from HIV-infected persons and from controls. These data indicated that the loss of CD4+ Th1 cell function in HIV-infected persons is not related to a Th1 to Th2 cytokine switch as previously proposed, but to a process of activation-induced death of CD4+ Th1 cells. Despite the absence of elevated levels of Th2 cytokines, apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented in vitro by antibodies to IL-10 or IL-4, two Th2 cytokines that downregulate Th1 cell responses, or by the addition of recombinant IL-12, a cytokine that upregulates Th1 functions. TCR-induced apoptosis of T cell hybridomas and preactivated T cells has been shown to involve the CD95 (Fas/Apo-1) molecule. CD4+ and CD8+ T cells from HIV-infected persons expressed high levels of the CD95 molecule, and, in contrast to T cells from controls, were highly sensitive to antibody-mediated CD95 ligation, which induced apoptosis in a percentage of T cells similar to that induced by TCR stimulation. As TCR-induced apoptosis, CD95-mediated apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented by the addition of recombinant IL-12. Together, these findings suggest that apoptosis of CD4+ T cells from HIV-infected persons involves an abnormal sensitivity to CD95 ligation, and to TCR stimulation in the presence of normal levels of Th2 cytokines. The preventive effect of IL-12 on both mechanisms has potential implications for the design of immunotherapy strategies aimed at the upregulation of CD4+ Th1 cell functions in AIDS.

Apoptosis↗

Influence of monosaccharide derivatives on liver cell glycosaminoglycan synthesis: 3-deoxy-D-xylo-hexose (3-deoxy-D-galactose) and methyl (methyl 4-chloro-4-deoxy-beta-D-galactopyranosid) uronate.

An improved, convenient synthesis of 3-deoxy-D-xylo-hexose (3-deoxy-D-galactose) has been developed, and the chemical synthesis of a novel monosaccharide derivative, methyl (methyl 4-chloro-4-deoxy-beta-D-galactopyranosid)uronate (compound 10), is described. Using primary hepatocytes in culture, each was used to explore its effect on glycosaminoglycan (GAG) synthesis. In the absence of analogues hepatocytes synthesize primarily (92-95%) heparan sulphate. At 1 mM, 3-deoxy-D-galactose had little observable effect on either liver cell GAG or protein synthesis. At 10 mM and 20 mM, 3-deoxy-D-galactose reduced [3H]glucosamine and 35SO4 incorporation into hepatocyte cellular GAGs to, respectively, 75% and 60% of the control cells. This inhibition of GAG synthesis occurred without any effect on hepatocyte protein synthesis, indicating that 3-deoxy-D-galactose's effect on GAG synthesis is not mediated through an inhibition of proteoglycan core protein synthesis. Furthermore, GAGs in the presence of 20 mM of the analogue were significantly reduced in size, 17 kDa vs. 66 kDa in untreated cells. These results reflect either impaired cellular GAG chain elongation, and/or altered GAG chain degradation. Compound 10 exhibited a concentration-dependent inhibition of both hepatocyte cellular GAG and protein synthesis. At concentrations of 5, 10 and 20 mM, compound 10 inhibited GAG and protein synthesis by 20, 65 and 90%, respectively. Exogenous uridine was able to restore partially the inhibition of protein synthesis, but was unable to reverse the effect of compound 10 on GAG synthesis. These results show that part of the effect of compound 10 on GAG synthesis is not mediated by an inhibition of proteoglycan core protein synthesis. GAGs in the presence of compound 10 are half as large as those in the absence of this compound (33 and 66 kDa, respectively). These results again may reflect either impaired cellular GAG chain elongation and/or altered GAG chain degradation. Potential metabolic routes for each analogue's effect are presented.

Animals↗

Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus.

Interleukin-10 (IL-10) is produced at a high level by B lymphocytes and monocytes of patients with systemic lupus erythematosus (SLE). In the present work, we analyzed whether this increased production of IL-10 contributed to the abnormal production of immunoglobulins (Ig) and of autoantibodies in SLE. The role of IL-10 was compared with that of IL-6, another cytokine suspected to play a role in these abnormalities. The spontaneous in vitro production of IgM, IgG, and IgA by peripheral blood mononuclear cells from SLE patients was weakly increased by recombinant IL (rIL)-6, but strongly by rIL-10. This production was not significantly affected by an anti-IL-6 mAb but was decreased by an anti-IL-10 mAb. We then tested the in vivo effect of these antibodies in severe combined immunodeficiency mice injected with PBMC from SLE patients. The anti-IL-6 mAb did not significantly affect the serum concentration of total human IgG and of anti-double-stranded DNA IgG in the mice. In contrast, the anti-IL-10 mAb strongly inhibited the production of autoantibodies, and, to a lesser extent, that of total human IgG. These results indicate that the Ig production by SLE B lymphocytes is largely IL-10 dependent, and that the increased production of IL-10 by SLE B lymphocytes and monocytes may represent a critical mechanism in the emergence of the autoimmune manifestations of the disease.

Adult↗

[Observations on the ultrastructure of non-amyloidotic fibrillary glomerulopathy].

Five patients with glomerulopathy and glomerular fibrillary protein deposits similar to those of amyloid but lacking the Congo red tinctorial affinity characterizing amyloid were studied. Clinically, these patients had severe proteinuria and microscopic hematuria, in addition, 2 patients had hypertension and renal function impairment. 5 renal biopsies were evaluated by light microscopy (LM), immunofluorescence (IF), immunoperoxidase (IP) and electron microscopy (EM). LM: mesangioproliferative, membranous (late stage) and membranoproliferative (late stage) patterns were seen in 2, 1 and 2 patients respectively. IF & IP: granular deposits, mainly of IgG, C3 and kappa, lambda light chains were found in all cases, either in mesangium and/or capillary walls. EM: randomly distributed fibrils with a diameter approximately 21nm (the diameter of amyloid fibrils is about 9.5nm) were found in glomerular basement membrane and/or mesangium. The pathologic findings suggested a new clinicopathological entity differentiated from amyloidosis. The relatively homogeneous nature of the immunoglobulin in the immune deposits is the basis for the fibril formation.

Adult↗

[In situ expression of intercellular adhesion molecule-1 in human glomerulonephritis].

We conducted immunocytochemical analysis with in situ hybridization technique to investigate the presence and role of intercellular adhesion molecule-1 (ICAM-1) in normal and diseased kidneys. A total of 64 renal biopsy specimens were classified in three groups according to the degree of cellular proliferation in glomerulus. Group A presented no or mild proliferation (n = 38). Group B showed definite proliferation (n = 21). Group C had glomerular sclerosis (n = 5). The ratio of cases exhibiting increased glomerular ICAM-1 expression in lupus nephritis (9/10) was significantly different from that in minimally changed disease (1/5) (P = 0.017). Glomerular ICAM-1 expression level correlated well with the cellular proliferation and infiltration in glomerulus (B&A: P < 0.001; C&B: P < 0.05). The percentage of cases with tubular ICAM-1 positivity in group B (81.0%) and group C (100%) was greater than that in group A (52.6%), which was also correlated with that of interstitial cell infiltration. In situ hybridization of 9 renal biopsies with digoxigenin labelled oligo probe proved immunocytochemical findings. We conclude that glomerular ICAM-1 expression level is correlated with inflammatory degree of glomerulus and that tubular ICAM-1 expression is associated with interstitial cell infiltration.

Gene Expression↗

[Hepatitis B virus, the main cause of membranous nephropathy in China].

To investigate the role of hepatitis B virus in the pathogenesis of membranous nephropathy (MN) in China, we studied 67 MN patients (excluding lupas nephritis V) with immunoperoxidase technique. In 46 (68.2%) of the 67 MN patients, HBV antigens (HBsAg, HBcAg and HBeAg) were detected in their glomeruli, and HBsAg, the dominant antigen was detected in 45 patients (67.2%). HBV-Ag was detected less frequently in the older MN group (33.3%) (> 50 years old) than in the two younger MN groups (73.1%, 75%) (< 30 years old, 30-50 years old) (P < 0.05). 30 randomly selected MsPGN patients were studied as controls. HBV antigens were detected in only 3 out of the 30 MsPGN patients. The HBV antigen positivity rate of the MN group was significantly higher than that of the MsPGN group (P < 0.01). The results suggested that HBV may be the main cause of MN in China, especially in those younger than 50 years, but not of MsPGN. HBsAg containing immune complexs (IC) may play an important role in the pathogenesis of HBV-MN.

Adolescent↗

[Clinical and pathological analysis of fibrillary glomerulopathy].

Four cases of fibrillary glomerulopathy (FGP) were reported for the first time in China. All patients had proteinuria, microscopic hematuria and hypertension. Renal function deteriorated in 2 cases. Pathological findings in light microscopy were sever: MPGN (2 cases), MN (1 case) and MsPGN (1 case). Congo-red stain of renal specimens was negative in all of them. Immunofluoscence (IF) in most of the cases (3/4 cases) showed granular IgG and C3 deposits in mesangium and glomerular basement membrane (GBM). Electron microscopy (EM) showed rich of fibrils distributed randomly over mesangium and GBM, the diameter of fibrils was 20.50 +/- 0.37nm. The diagnosis of FGP depends on EM examination. The actual incidence of FGP in China needs further studies.

Adult↗

[Cloning and expression of beta-glucosidase gene in Xanthomonas campestris XA5-5].

A beta-glucosidase gene from Xanthomonas campestris XA5-5 was cloned in Escherichia coli with the broad-host-range plasmid pRK404. The beta-glucosidase encoding plasmid designated pLZS1 contained a 1.1kb PstI DNA fragment deriving from XA5-5. The plasmid pLZS1 was transconjugated by filter mating into XA5-5 producing homologous clones XA5-5(pLZS1). Plasmid stability analysis revealed that pLZS1 was more stable in XA5-5 than in E. coli JM83. The level of beta-glucosidase expressed in XA5-5 (pLZS1) was much higher than in E. coli JM83 (pLZS1) using salicin as the substrate. From the results obtained, it seems that the gene product of this cloned DNA fragment has higher affinity to salicin substrate, and in some sense reduces the affinity between the enzyme and pNPG substrate in XA5-5.

Cloning, Molecular↗

Intravitreal pharmacokinetics of liposome-encapsulated amikacin in a rabbit model.

BACKGROUND: Intravitreal injection of antibiotics has become a standard therapy for bacterial endophthalmitis. The duration of effective antimicrobial levels in the vitreous after single injection, however, may not be long enough to get optimal response. The authors prepared liposome-encapsulated amikacin for prolonging the duration of intravitreal therapeutic concentrations and investigated the intravitreal pharmacokinetics of the liposomes and amikacin in phosphate buffer solution (PBS) as control. METHODS: The liposome-encapsulated amikacin was prepared by reverse-phase evaporation method. The intravitreal pharmacokinetics of the liposomes was compared with amikacin in PBS by fluorescence polarization immunoassay. Albino rabbits were randomly distributed into 12 groups. Rabbits in groups 1 to 6 and in groups I to VI (control groups) received an intravitreal injection of the liposome-encapsulated amikacin and amikacin in PBS, respectively. RESULTS: The encapsulation rate of amikacin was 91%. The time of 50% spontaneous degradation (half-life) of the liposomes in PBS (38 degrees C, pH 7.4) was 47.6 days, and the time of 50% release (half-life) of the drug from the liposomes in PBS was 84.8 hours. The vitreous amikacin concentrations in groups 1 to 6 were significantly greater (P < 0.05) than those in control groups I to VI in every time interval, except in groups 1 to 3 at 1 hour after injection. The difference was particularly obvious in the endophthalmitis groups. The clearance of encapsulated amikacin in vitreous appeared to be related to the state of blood-ocular barrier and to the structural integrity of vitreous. The distribution, the absorption, and the elimination of encapsulated amikacin in vitreous showed the first-order kinetics. CONCLUSION: The liposome-encapsulated amikacin prolonged half-life of the drug in vitreous. The results of the pharmacokinetic analysis suggested that in endophthalmitis, especially in severe cases, the liposomes may be preferable to conventional preparation.

Absorption↗

Tumor necrosis factor-alpha mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism.

Osteoblasts or bone marrow stromal cells are required as supporting cells for the in vitro differentiation of osteoclasts from their progenitor cells. Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) in the presence of macrophage colony-stimulating factor (M-CSF) is capable of replacing the supporting cells in promoting osteoclastogenesis. In the present study, using Balb/c-derived cultures, osteoclast formation in both systems-osteoblast/bone-marrow cell co-cultures and in RANKL-induced osteoclastogenesis-was inhibited by antibody to tumor necrosis factor-alpha (TNF-alpha), and was enhanced by the addition of this cytokine. TNF-alpha itself promoted osteoclastogenesis in the presence of M-CSF. However, even at high concentrations of TNF-alpha the efficiency of this activity was much lower than the osteoclastogenic activity of RANKL. RANKL increased the level of TNF-alpha mRNA and induced TNF-alpha release from osteoclast progenitors. Furthermore, antibody to p55 TNF-alpha receptors (TNF receptors-1) (but not to p75 TNF-alpha receptors (TNF receptors-2) inhibited effectively RANKL- (and TNF-alpha() induced osteoclastogenesis. Anti-TNF receptors-1 antibody failed to inhibit osteoclastogenesis in C57BL/6-derived cultures. Taken together, our data support the hypothesis that in Balb/c, but not in C57BL/6 (strains known to differ in inflammatory responses and cytokine modulation), TNF-alpha is an autocrine factor in osteoclasts, promoting their differentiation, and mediates, at least in part, RANKL's induction of osteoclastogenesis.

Acid Phosphatase↗