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Biomedical subjects

M H Zhao

Publications and source records attributed to M H Zhao.

At least 19 recordsLinked to original sources
PubMed2005

Clinical [corrected] and pathological characteristics of Chinese patients with antineutrophil cytoplasmic autoantibody associated systemic vasculitides: a study of 426 patients from a single centre.

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) are serological markers of ANCA associated systemic vasculitides (AASV), which is one of the most common multisystem autoimmune diseases. Features of Chinese patients with AASV have not been fully investigated. OBJECTIVE: To analyse the clinical and pathological characteristics of Chinese patients with AASV. METHODS: 426 Chinese patients with AASV diagnosed in the past eight years were retrospectively studied and their clinical and pathological data were analysed. RESULTS: Of the 426 patients, 87 (20.4%) were Wegener's granulomatosis, 337 (79.1%) were microscopic polyangiitis and two (0.5%) were Churg-Strauss syndrome. Only 201 of 426 (47.2%) patients were diagnosed within three months. Clinically, the patients had multisystem involvement. Altogether 371 of 426 (87.1%) had kidney involvement and 260 of 426 (61.0%) had lung involvement. The prevalences of renal involvement and fatigue were significantly higher in patients with MPO-ANCA than that in patients with PR3-ANCA; the prevalences of ophthalmic, nasal involvement, rash, and arthragia were significantly higher in patients with PR3-ANCA than those in patients with MPO-ANCA. The one and five year death rates were 13.1% and 22.4%, respectively. The percentage of patients progressing to end stage renal disease at one and five years was 15.9% and 27.1%, respectively. CONCLUSIONS: AASV is not a rare autoimmune disease in Chinese people. Kidney and lung were the most vulnerable organs. For patients with multiorgan damage, an ANCA test should be performed to make an early diagnosis and to start treatment in time.

Adolescent↗
PubMed2000

[Multi-bed & multi-parameter central monitoring system based on TCP/IP protocol].

Communication is one of the key problems to a central monitoring system. In this paper we put forward a central monitoring system using TCP/IP as the network protocol, Windows NT4.0 as the platform, forming a Intranet in a hospital. We also discussed the communication problem between the bed-side monitoring station and the central monitoring station in detail and then put forward a new protocol--Hospital Central Monitor Protocol (HCMP) based on TCP/IP to transfer monitoring data. It is easy to achieve tele-monitoring through the current communication subsystem.

Computer Communication Networks↗
PubMed1998

Effect of intrauterine injection of chlorpromazin on implantation in the rat.

In rats, injection of chlorpromazin hydrochloride (CPZ), a calmodulin antagonist, to each uterine horn had a significant (87%) anti-implantation effect and 100% antifertility effect. Both of these rates were zero in the saline control group. Polyacrylamide gel electrophoresis analysis of the uterine fluid showed a decrease in the protein content and certain changes in its chemical composition, in particular, a marked reduction in the number of bands of estradiol-induced 70 kD proteins in the experimental group. No significant difference was found in the ovarian weight and the serum estradiol (E2) and progesterone (P) levels between the two groups. These results suggest that calmodulin influences the process of implantation and this effect is not directly related to the serum concentrations of E2 and P. It is believed that CPZ probably exerted its anti-implantation effect by a direct action on the uterus.

Animals↗
PubMed1998

Catalase and alpha-enolase: two novel granulocyte autoantigens in inflammatory bowel disease (IBD).

In IBD, the target antigens of anti-neutrophil cytoplasmic autoantibodies (ANCA) have not been fully identified, which limits the analysis of the diagnostic significance as well as of the possible pathophysiological role of these antibodies. In this study, we identify the target antigens of ANCA in large groups of patients with ulcerative colitis (UC) and Crohn's disease (CD). Apart from antibodies against lactoferrin and bactericidal/permeability-increasing protein (BPI), which have been reported before, antibodies against two novel granulocyte antigens were identified: antibodies against a 57/56-kD doublet were found in 38% of samples from UC patients and in 26% of samples from CD patients, whereas antibodies against a 47-kD protein were found in 10% of samples from UC patients and in 18% of samples from CD patients. Partial purification and amino acid sequence analysis identified the 57-kD protein as catalase and the 47-kD protein as alpha-enolase. This study is the first to report catalase and alpha-enolase as granulocyte antigens for autoantibodies in IBD.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Antineutrophil cytoplasmic autoantibodies (ANCA) and their target antigens in Chinese patients with lupus nephritis.

BACKGROUND: ANCA have been found in patients with systemic lupus erythematosus (SLE); however, the prevalence of ANCA and their target antigens is still not certain. This study is to investigate the prevalence of ANCA and their target antigens in Chinese patients with lupus nephritis. METHODS: Ninety-five serum samples were collected from 95 renal-biopsy-proven lupus nephritis patients. Indirect immunofluorescence using ethanol-fixed leukocytes as substrate and ELISA using six highly purified known ANCA antigens as solid-phase ligands were performed. The specific ANCA antigens included proteinase 3, myeloperoxidase, bactericidal/permeability-increasing protein, human leukocyte elastase, cathepsin G, and lactoferrin. The prevalence of ANCA in patients with (n=65) and without (n=30) active renal pathological lesions was also compared to reveal whether ANCA correlates with disease activity. RESULTS: (i) None of the sera recognized proteinase 3, myeloperoxidase, and human leukocyte elastase, and only one serum recognized bactericidal/permeability-increasing protein. The striking finding was that 59/95 (62.1%) sera recognized cathepsin G and the titres of some sera reached 1/3200. Eight of 95 sera (8.4%) recognized lactoferrin. (ii) The percentage of anti-cathepsin G antibody positive samples in patients with active renal lesions was significantly higher than in patients without active lesions (73.4 vs 36.7%, P<0.0001), whereas, anti-lactoferrin antibodies had no correlation with active renal lesions. (iii) By indirect immunofluorescence, only 22% of the 95 sera were ANCA positive. CONCLUSIONS: Our results suggest that the majority of lupus nephritis patients have ANCA and that the major target antigens is cathepsin G. Anti-cathepsin G antibodies seem to be correlated with renal disease activity.

Adolescent↗
PubMed1997

Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls. RESULTS: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01). CONCLUSION: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.

Adult↗
PubMed1997

Vasculitis and bronchiectasis in a patient with antibodies to bactericidal/permeability-increasing protein and alpha1-antitrypsin deficiency.

A patient with alpha1-antitrypsin deficiency is reported herein; this subject developed aggressive bronchial disease and recurrent cutaneous vasculitis after pulmonary infection with Pseudomonas aeruginosa. Autoantibodies to neutrophil cytoplasmic antigens were detected, which produced granular cytoplasmic staining by indirect immunofluorescence with specificity for a newly characterized antigen: bactericidal/permeability-increasing protein (BPI). The bronchial disease and vasculitis improved, and the IgA anti-BPI titer fell after antipseudomonal treatment. This raises the possibility that anti-BPI antibodies contributed to both the bronchial disease and vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

[Effect of SR-140333, a tachykinin NK-1 antagonist, on antigen-induced airway hyperresponsiveness in sensitized rats].

In the present study, the effects of SR-140333, ((S)-1-(2-[3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin- 3yl]ethyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane.chloride), a nonpeptide antagonist for tachykinin NK-1 receptor, on the antigen-induced airway response to methacholine (MCh) aerosol and airway inflammation in sensitized SD rats were investigated. The baseline respiratory frequencies, tachypnea response to methacholine(MCh), the -log PC30 values of MCh and the leukocyte counts in bronchoalveolar lavage significantly increased after inhalation of 1% oval albumin(OA) aerosol. SR-140333 (152 nmol.kg-1, i.p.) or dexamethasone(368 nmol.kg-1, i.p.), bid x 3 d inhibited these responses. SR-140333 at a low dose of 0.01 mg.kg-1 showed an incomplete inhibition. From these results, we conclude that antigen challenge causes airway hyperresponsiveness and airway inflammation and that tachykinin NK-1 receptor antagonist inhibits these responses.

Animals↗
PubMed1996

A comprehensive method to purify three major ANCA antigens: proteinase 3, myeloperoxidase and bactericidal/permeability-increasing protein from human neutrophil granule acid extract.

Indirect immunofluorescence (IIF) techniques have shown that anti-neutrophil cytoplasm autoantibodies (ANCA) are useful serological markers for certain small vessel vasculitides and the non-vasculitic inflammatory disorders. ELISA procedures, using purified molecules as solid phase ligands, helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two major ANCA antigens; and recently we characterised bactericidal/permeability-increasing protein (BPI) as another important ANCA antigen. ANCA against these three antigens are associated with different clinical disorders. Therefore purified antigens are needed to determine these different autoantibody specificities in order to help diagnosis and guide treatment. Here we describe a method using Orange-A dye ligand chromatography and cation exchange chromatography for the sequential purification of PR3, MPO and BPI, from the same starting material, an acid extract of normal human neutrophil granules. After separation the three antigens were free of contamination by each other and no traces were found of other known minor ANCA antigens.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis.

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG, and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability-increasing protein (BPI), a recently-characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI & FEV1: r = -0.508, p < 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (n = 6) than in those without (p < 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.

Adolescent↗
PubMed1996

Azurocidin is a novel antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in systemic vasculitis.

We isolated a 27-kD protein using cation exchange chromatography from an acid extract of neutrophil granules. N-terminal amino acid sequence analysis of the first 10 residues showed that this protein is azurocidin, a member of the family of neutral serine proteinase found in the neutrophil, which shares amino acid sequence homology with the three other neutral serine proteinases, elastase, proteinase 3 (PR3) and cathepsin G, but unlike them is without proteolytic activity. To test whether, in addition to these proteases, azurocidin might be a target for the humoral autoimmune responses associated with human vasculitis, 185 indirect immunofluorescence (IIF)-positive ANCA sera, made up of four groups of sera with specificities for PR3 (n=37), myeloperoxidase (MPO; n=50), bactericidal/permeability-increasing protein (BPI; n=41) and sera that recognized none of them (triple negative, n=57), and 46 normal sera were screened for IgG anti-azurocidin antibodies using an ELISA incorporating purified azurocidin. Twenty of the 185 IIF-positive sera and 2/46 normal sera displayed reactivity with azurocidin. Positive sera could blot the 27-kD band by Western blot analysis. Further study of the 20 positive sera revealed that: (i) 10 also had autoreactivity for MPO, of which six additionally recognized lactoferrin; (ii) two had reactivity with BPI; (iii) the remaining eight sera were positive only for azurocidin. All 20 sera were from patients with systemic vasculitis, and four of the six sera with triple reactivity (for azurocidin, MPO and lactoferrin) were from patients with hydralazine-induced vasculitis. We concluded that: (i) azurocidin is a novel ANCA antigen; (ii) anti-azurocidin antibodies from a subgroup of patients might represent the consequence of a drug-induced multi-clone activation.

Adult↗
PubMed1996

ANCA associated with Behçet's disease.

Behçet's disease is a multisystem disorder affecting primarily mucocutaneous and ocular sites although the gastrointestinal, cardiovascular, central nervous and respiratory systems may also be involved. Hulusi Behçet, a Turkish dermatologist, first described Behçet's disease in 1937 and suggested a possible infectious aetiology. The pathogenesis of this condition still remains unclear although it is likely that infection acts as a trigger in genetically susceptible individuals. We report a patient with unusual cutaneous manifestations of Behçet's disease and antineutrophil cytoplasmic antibodies (ANCA) directed against the cytotoxic protein, bactericidal/permeability-increasing protein (BPI). This is the first report of Behçet's disease associated with this autoantibody.

Adult↗
PubMed1996

[Effect of shengmaisan on serum lipid peroxidation in acute viral myocarditis].

The effect of Shengmaisan (SMS) on 62 acute viral myocarditis patients and its peroxidation damage was studied. The results revealed that the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in blood were decreased and the content of malondialdehyde (MDA) in plasma was increased in acute viral myocarditis patients in comparison with the healthy controls (P < 0.001). 62 acute viral myocarditis patients were divided into two groups: SMS group and placebo group. After treatment, both SOD and GSH-Px activities were increased and the level of MDA decreased (P < 0.001) in SMS group, while those in placebo group were not changed (P < 0.05). The results suggested that the myocardial damage of viral myocarditis is closely related with lipid peroxidation SMS acts as an effective free radical scavenger and anti-lipid peroxidation drug. SMS could prevent the damage of myocardia and might be taken as one of the effective therapeutic methods in treatment of acute viral myocarditis.

Adolescent↗
PubMed1995

Distribution of MHC class II alleles in primary systemic vasculitis.

Previous studies have shown a number of different associations between major histocompatibility complex (MHC) alleles and primary systemic vasculitis. Disease heterogeneity and the lack of specificity of certain MHC typing techniques may have contributed to the lack of consistency in those studies. We therefore studied a relatively homogeneous group of 94 patients with Wegener's granulomatosis, microscopic polyangiitis, or renal-limited vasculitis using molecular techniques that allow more precise assignment of MHC genotype. DNA was prepared from peripheral blood and DRB1 genotype determined by Taq restriction fragment length polymorphism. DQB1 and DPB1 genotype were assigned by polymerase chain reaction amplification followed by probing with allele-specific oligonucleotides. Specificity of associated anti-neutrophil cytoplasm antibodies (ANCA) was determined where possible by solid phase immunoassays using purified proteinase 3 (PR3) and myeloperoxidase (MPO). After correction for multiple comparisons there were no significant differences in the distribution of DRB1, DQB1 and DPB1 alleles between a local control group (N = 90 for DRB1, N = 50 for DQB1 and DPB1) and the patient group as a whole (N = 94) or two a priori defined subgroups (anti-PR3 positive, N = 35; anti-MPO positive, N = 22). We have therefore found no significant association between primary systemic vasculitis and any MHC class II allele. This, together with the fact that previous smaller studies have shown no consistent association, suggests that any such association is very weak, if it exists at all.

Alleles↗
PubMed1995

Antineutrophil cytoplasm autoantibodies and vasculitis.

Antineutrophil cytoplasm autoantibodies are useful diagnostic serologic markers for a variety of well-known primary vasculitic syndromes, including Wegener's granulomatosis, microscopic polyangiitis, and idiopathic necrotizing and crescentic glomerulo-nephritis. More recently antineutrophil cytoplasm autoantibodies have been found in other vasculitic syndromes, such as Churg-Strauss syndrome, Henoch-Schönlein purpura, and some nonvasculitic diseases such as rheumatoid arthritis, inflammatory bowel disease, and autoimmune hepatobiliary diseases. There is now evidence to suggest that infection might be an important etiologic factor in the development of antineutrophil cytoplasm autoantibody-associated vasculitides. This link has been strengthened by in vitro data that suggest that antineutrophil cytoplasm autoantibodies are directly involved in the pathogenesis of antineutrophil cytoplasm autoantibody-associated vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1995

Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis.

Indirect immunofluorescence (IIF) techniques have shown that ANCA are useful serological markers for some small vessel vasculitides, and ELISA assays, using purified molecules as solid-phase ligand, have helped to identify proteinase 3 (PR3) and myeloperoxidase (MPO) as two of the major ANCA antigens. There remain a substantial number of serum samples, which are positive by IIF, yet recognize neither PR3 nor MPO (double-negative samples). We found, by Western blot analysis of soluble neutrophil granule proteins, that certain of these double-negative samples recognized a 55-kD doublet of which the first eight residues shared N-terminal amino acid sequence homology with BPI, a potent antibiotic towards Gram-negative bacteria. We developed a simple, quick and robust two-step immunobiochemical method to purify BPI. This was then employed to detect anti-BPI autoantibodies by ELISA and Western blot analysis. We tested 100 double-negative samples and 400 consecutive new samples sent for routine ANCA testing in the anti-BPI ELISA. We found that 45 of the 100 double-negative and 44 of the 400 new routine samples recognized BPI. By Western blot analysis 20/20 positive anti-BPI samples blotted the 55-kD protein. Inhibition assays confirmed the specificity of binding. Review of the 89 anti-BPI-positive patients showed a male dominance (M:F ratio 55:34), a mean age of 60.4 years and clinical diagnoses ranging from organ limited vasculitis to widespread systemic vasculitis.

Adolescent↗
PubMed1995

Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries.

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.

Amino Acid Sequence↗