Biomedical subjects

M X Zhang

Publications and source records attributed to M X Zhang.

17 recordsLinked to original sources

PubMed2006

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes.

OBJECTIVE: The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.

Adiponectin↗

PubMed2001

Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis.

The incidence of life-threatening, hematogenously disseminated candidiasis, which is predominantly caused by Candida albicans, parallels the use of modern medical procedures that adversely affect the immune system. Limited antifungal drug choices and emergence of drug-resistant C. albicans strains indicate the need for novel prevention and therapeutic strategies. We are developing vaccines and Abs that enhance resistance against experimental candidiasis. However, the prevalence of serum anti-Candida Abs in candidiasis patients has led to the misconception that Abs are not protective. To explain the apparent discrepancy between such clinical observations and our work, we compared functional activities of C. albicans-specific protective and nonprotective mAbs. Both kinds of Abs are agglutinins that fix complement and are specific for cell surface mannan, but the protective Abs recognize beta-mannan, and the nonprotective Ab is specific for alpha-mannan. By several indirect and direct measures, the protective mAbs more efficiently bind complement factor C3 to the yeast cell than do nonprotective Ab. We hypothesize that the C3 deposition causes preferential association of blood-borne fungi with host phagocytic cells that are capable of killing the fungus. We conclude from these results that the protective potential of Abs is dependent on epitope specificity, serum titer, and ability to rapidly and efficiently fix complement to the fungal surface. The mechanism of protection appears to be associated with enhanced phagocytosis and killing of the fungus.

Animals↗

PubMed2001

[Study on endothelial dysfunction and platelet activation in elderly hypertensive patients complicated with cerebral infarction].

OBJECTIVE: The aim of this paper was to investigate endothelial dysfunction, platelet activation, and inflammation in elderly hypertensive patients and those complicated with cerebral infarction. METHODS: Twenty-eight elderly hypertensive patients complicated with cerebral infarction(within 72 hours after onset of neurological symptoms), thirty-one Stage I-II elderly hypertensive patients and twenty-eight elderly healthy individuals were selected as subjects. Their plasma concentrations of von Willebrand factor(vWF), alpha granule membrane protein-140(GMP-140), and serum concentrations of C-reaction protein(CRP) were examined. RESULTS: Elderly hypertensive patients complicated with cerebral infarction had significantly higher plasma vWF, GMP-140, and serum CRP than elderly hypertensive patients and elderly healthy individuals. Plasma vWF and GMP-140 were higher in elderly hypertensive patients than elderly healthy individuals, whereas serum CRP was increased slightly and there was no significant difference between elderly hypertensive patients and elderly healthy individuals. CONCLUSION: This study suggests that elderly hypertensive patients complicated with cerebral infarction have obvious endothelial dysfunction, platelet activation, and inflammatory change. Stage I-II elderly hypertensive patients have obvious endothelial dysfunction and platelet activation as well.

Aged↗

PubMed2001

Role of glucan and surface protein BAD1 in complement activation by Blastomyces dermatitidis yeast.

Our previous studies showed that Blastomyces dermatitidis yeast activates the human complement system, leading to deposition of opsonic complement fragments onto the yeast surface. This report examines the influence of altered surface expression of glucan or BAD1 protein (formerly WI-1) on the yeast's ability to activate and bind C3. Compared to the wild type, a glucan-deficient mutant yeast delayed initiation of C3 deposition and reduced C3-binding capacity by 50%. Linkage of baker's-yeast beta-glucan to the glucan-deficient yeast restored initial C3 deposition kinetics to the wild-type level and partially restored C3-binding capacity, suggesting that beta-glucan is an initiator of complement activation and a C3 acceptor. The role of BAD1 in B. dermatitidis yeast-complement interaction was also assessed. BAD1 knockout yeast initiated faster C3 deposition and increased C3-binding capacity compared to the wild-type yeast or a BAD1-reconstituted yeast, suggesting either a lack of an intrinsic ability in BAD1 or an inhibitory role of BAD1 in complement activation and binding. However, both complement activation and the capacity for C3 binding by the wild-type yeast were enhanced in normal human serum supplemented with an anti-BAD1 monoclonal antibody (MAb) or in immune sera from blastomycosis patients. Microscopic analysis revealed that more initial C3-binding sites were formed on yeast in the presence of both naturally occurring complement initiators and exogenous anti-BAD1 MAb, suggesting that anti-BAD1 antibody enhanced the ability of B. dermatitidis yeast to interact with the host complement system. Thus, glucan and BAD1 have distinctly different regulatory effects on complement activation by B. dermatitidis.

Blastomyces↗

PubMed2001

Immunohistochemical demonstration of alpha1,4-N-acetylglucosaminyltransferase that forms GlcNAcalpha1,4Galbeta residues in human gastrointestinal mucosa.

alpha1,4-N-acetylglucosaminyltransferase (alpha4GnT) is a glycosyltransferase that mediates transfer of GlcNAc to betaGal residues with alpha1,4-linkage, forming GlcNAcalpha1--> 4Galbeta-->R structures. In normal human tissues, glycoproteins having GlcNAcalpha1-->4Galbeta-->R structures at non-reducing terminals are exclusively limited to the mucins secreted from glandular mucous cells of gastric mucosa, Brunner's gland of duodenum, and accessory gland of pancreaticobiliary tract. Recently, we have isolated a cDNA encoding human alpha4GnT by expression cloning. Although alpha4GnT plays a key role in producing this unique glycan in vitro, the actual localization of alpha4GnT was not determined. In this study we examined the localization of alpha4GnT in various human tissues, including gastrointestinal mucosa, using a newly developed antibody against human alpha4GnT. The specificity of the antibody was confirmed by analyses of human gastric adenocarcinoma AGS cells transfected by alpha4GnT cDNA. Expression of alpha4GnT was largely associated with the Golgi region of mucous cells that produce the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R, such as the glandular mucous cells of stomach and Brunner's gland. An immunoprecipitation experiment disclosed that two distinct mucin proteins, MUC5AC and MUC6 present in gastric mucin, carried the GlcNAcalpha1-->4Galbeta-->R structures. These results indicate that alpha4GnT is critical to form the mucous glycoproteins having GlcNAcalpha1-->4Galbeta-->R on MUC6 and MUC5AC in vivo.(J Histochem Cytochem 49:587-596, 2001)

Animals↗

PubMed2001

[Intracellular potential changes in crucian carps Mauthner cells evoked by vagal sensory inputs].

In the present experiments, microelectrode recording technique was used to explore the electrophysiological properties of Mauthner cells (M-cells) with stimuli applied to the right vagus. Direct stimulation of the right vagus evoked short-latency, long-lasting, graded, and complex postsynaptic potentials (PSPs) on both Mauthner cell bodies in crucian carp, which are stimulus strength- and frequency- dependent. The evoked PSPs reduced the amplitudes of the antidromic action potentials. After intramuscular injection of strychnine, both amplitude and averaged duration of the PSPs increased, on which two or more action potentials were superimposed. The results suggest that the afferent pathways from vagus to M-cells are mediated by several neuron chains with different numbers of relayed synapses, and they may be excitatory and/or inhibitory in nature. Therefore vagus input would modulate the excitability of the M-cells.

Action Potentials↗

PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗

PubMed1998

A case-control study of hepatitis B and C virus infection as risk factors for hepatocellular carcinoma in Henan, China.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and is particularly prevalent in China. China is also a hyperendemic area for hepatitis B virus (HBV) infection. Although a strong association between HBV infection and HCC has been established previously, the role of hepatitis C virus (HCV) infection and the interaction between HBV and HCV in the development of HCC has not been adequately explored. The major objective of this study is to determine the relationship between HBV or HCV infection and HCC by use of case-control study in Henan, China. METHOD: In all, 152 HCC patients and 115 control patients were collected from four hospitals in Henan, China between January 1994 and October 1995. The demographic characteristics of the two groups were comparable. In further analysis, a 1:1 pair-matched case-control study was performed. Of 152 HCC patients, 113 were randomly selected to be pair-matched by sex and age (+/-5 years) to controls with non-hepatic disease. All the cases and controls were interviewed during hospitalization by two specially trained interviewers using a standard questionnaire. All sera were tested for HBV and HCV markers. Odds ratios (OR) and 95% CI for HCC risk factors were calculated by logistic regression model controlling for possible confounding factors such as sex and age. The multivariate analysis was done on the basis of the univariate analysis. RESULTS: The results of this study indicated that the prevalence of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were much higher in HCC patients (63.2% and 11.2% respectively) than in the control patients (5.2%, 3.5%). The difference between two groups was significant (P < 0.05). Risk factor analysis revealed that both HBV and HCV infection were important factors for HCC in Henan, China and HBV appeared to have a key role in the development of HCC. Odds ratios of HBsAg and HBV infection were 28.82 (95% CI: 11.18-78.78) and 31.22 (95% CI: 13.86-72.15), respectively. Moreover, the risk of developing HCC increased significantly and showed an additive effect when both viral markers of HBV and HCV infection were considered (OR = 42.85). Results from the 1:1 pair-matched case-control study also showed that HBV infection was an important risk factor for HCC, which was consistent with the results from the group-matched case-control study. CONCLUSION: This is the first reported case-control study of HCC in Henan, China. This study provides further evidence that chronic HBV infection is strongly associated with the development of HCC among this population. Our results have demonstrated that HCV and HBV infection are independent and probably additive risk factors for HCC.

Adult↗

PubMed1998

Mannan-specific immunoglobulin G antibodies in normal human serum accelerate binding of C3 to Candida albicans via the alternative complement pathway.

Candida albicans activates the classical and alternative complement pathways, leading to deposition of opsonic complement fragments on the cell surface. Our previous studies found that antimannan immunoglobulin G (IgG) in normal human serum (NHS) allows C. albicans to initiate the classical pathway. The purpose of this study was to determine whether antimannan IgG also plays a role in initiation of the alternative pathway. Pooled NHS was rendered free of classical pathway activity by chelation of serum Ca2+ with EGTA alone or in combination with immunoaffinity removal of antimannan antibodies. Kinetic analysis revealed a 6-min lag in detection of C3 binding to C. albicans incubated in EGTA-chelated NHS, compared to a 12-min lag in NHS that was both EGTA chelated and mannan absorbed. The 12-min lag was shortened to 6 min by addition of affinity-purified antimannan IgG. The accelerating effect of antimannan IgG on alternative pathway initiation was dose dependent and was reproduced in a complement binding reaction consisting of six purified proteins of the alternative pathway. Both Fab and F(ab')2 fragments of antimannan IgG facilitated alternative pathway initiation in a manner similar to that observed with intact antibody. Immunofluorescence analysis showed that addition of antimannan IgG to EGTA-chelated and mannan-absorbed serum promoted an early deposition of C3 molecules on the yeast cells but had little or no effect on distribution of the cellular sites for C3 activation. Thus, antimannan IgG antibodies play an important regulatory role in interactions between the host complement system and C. albicans.

Antibodies, Fungal↗

PubMed1998

Contrasting roles of mannan-specific monoclonal immunoglobulin M antibodies in the activation of classical and alternative pathways by Candida albicans.

Polyclonal antimannan immunoglobulin G (IgG) activates the classical complement pathway and accelerates initiation of the alternative pathway by Canidida albicans. This dual role was assessed for two antimannan IgM monoclonal antibodies (MAbs). MAb B6.1 is specific for an epitope on the acid-labile portion of C. albicans phosphomannan; MAb B6 is specific for an epitope on the acid-stable region. Both MAbs were potent activators of the classical pathway but poor facilitators of alternative pathway initiation.

Antibodies, Monoclonal↗

PubMed1997

Activation, binding, and processing of complement component 3 (C3) by Blastomyces dermatitidis.

Complement plays a key role in phagocyte recognition and killing of Blastomyces dermatitidis, but little is known about how complement components interact with the yeast. We report the characteristics of activation, binding, and processing of C3 by B. dermatitidis. In pooled normal human serum (NHS), deposition of C3 on the yeast was detectable within 2 min, whereas in NHS containing MgEGTA, deposition was delayed by 6 min, indicating that the yeast activates C3 by both classical and alternative pathways. When both pathways were operative, maximal binding of 4.5 x 10(6) C3 molecules/cell was achieved in less than 30 min. In the absence of the classical pathway, yeast cells bound 80% of the maximum C3, indicating that the yeast intrinsically activates the alternative pathway. Delayed deposition of C3 in NHS-MgEGTA was similar to that in NHS preabsorbed by the yeast or by immobilized protein A/G to remove serum immunoglobulin. Purified immunoglobulin restored C3 binding to NHS preabsorbed by the yeast, suggesting that antibody in nonimmune serum initiates the classical pathway. beta-Glucan absorption of NHS abolished the classical pathway, suggesting that cell wall beta-glucan is a target of initiating antibodies. Hydroxylamine treatment of NHS-opsonized yeast cells showed that 76% of C3 was bound to yeast cells by ester linkage, supporting a role for hydroxyl groups on cell wall polysaccharides. Hydroxylamine-cleaved fragments were chiefly C3b and iC3b; 70% of hydroxylamine-sensitive C3b was converted to iC3b within 1 min of opsonization, and the ratio was stable over 1 h. Our data predict that C3b and iC3b on opsonized yeast cells direct binding to CR1 and CR3 receptors on human phagocytes, which, in turn, may influence the fate of this host-pathogen interaction.

Blastomyces↗

PubMed1997

Mannan-specific immunoglobulin G antibodies in normal human serum mediate classical pathway initiation of C3 binding to Candida albicans.

Candida albicans activates both the classical and alternative complement pathways. Previous studies found that immunoglobulin G (IgG) in normal human serum (NHS) mediates classical pathway initiation. The goal of this study was to determine the role of candidal mannan-specific human IgG antibodies in complement activation. Mannan was purified from the yeast cells, and naturally occurring antimannan IgG was isolated from pooled NHS or plasma samples by immunoaffinity chromatography. Early activation and binding of C3, characteristics of classical pathway activity, were abolished in yeast- or mannan-absorbed serum but could be restored to absorbed serum with added purified antimannan IgG in a dose-dependent manner. Microscopically, the immunofluorescence pattern of initial C3 binding was diffuse over the entire cell surface for yeast cells incubated in NHS or in mannan-absorbed NHS supplemented with antimannan IgG but was asynchronous and focal for yeast cells incubated in EGTA-treated or mannan-absorbed NHS. The antimannan IgG level in serum samples from 21 donors varied from 17 to 570 microg/ml of serum compared to 220 microg in pooled NHS samples. The rate of initial C3 binding to yeast cells correlated with the level of antimannan IgG in sera from different individuals (r2 = 0.94) and could be accelerated in sera containing lower amounts of antimannan IgG with exogenous antimannan IgG. These observations identify antimannan IgG as the initiator of classical pathway C3 deposition on C. albicans. Given the variability in the levels of antimannan antibodies in sera from different individuals, the presence or absence of these antibodies may be an important determinant of host resistance to disseminated candidiasis.

Antibodies, Fungal↗

PubMed1996

A role for the disulfide bond spacer region of the Chlamydomonas reinhardtii coupling factor 1 gamma-subunit in redox regulation of ATP synthase.

The gamma-subunit of chloroplast coupling factor 1 contains a disulfide bond which is involved in the redox regulation of the enzyme. In all the sequence plant gamma-subunits this disulfide bond is separated by a five amino acid spacer region. To investigate the regulatory significance of this region genetic transformation experiments were performed with Chlamydomonas reinhardtii. C. reinhardtii strain atpC1 (nitl-305, cw 15, mt-), which does not accumulate the CF1 gamma-subunit polypeptide, was independently transformed with two constructs, each bearing mutations within the disulfide bond spacer region between Cys198 and Cys204 of the gamma-subunit. Successful complementation was confirmed by phenotypic selection, Northern blot analysis, and reverse transcription polymerase chain reaction. Whereas wild-type thylakoid membrane particles catalyze in vitro, PMS-dependent photophosphorylation that is stimulated 2-fold by the addition of DTT, similar particles from each of the mutant strains exhibit rates of ATP synthesis that are independent of DTT. Consistent with these results, wild-type CF1 ATPase activity is stimulated by DTT which is in contrast to the ATPase activities of both the mutant strains which are independent of DTT addition. These results suggest a role of the gamma-subunit disulfide bond spacer region in the redox regulation of chloroplast ATP synthase.

Amino Acid Sequence↗

PubMed1995

Role of the Chlamydomonas reinhardtii coupling factor 1 gamma-subunit cysteine bridge in the regulation of ATP synthase.

The gamma-subunit of coupling factor 1 (CF1) contains a cysteine bridge that is thought to be involved in the redox control of enzymatic activity. In order to test the regulatory significance of this disulfide bond, genetic transformation experiments with Chlamydomonas reinhardtii were performed. C. reinhardtii strain atpC1 (nit1-305, cw 15, mt-), which is null for the gamma-subunit, was transformed and complemented with gamma-subunit constructs containing amino acid substitutions localized to the cysteine bridge between Cys198 and Cys204. Successful complementation was confirmed by phenotypic selection, Northern blot analysis, reverse transcription polymerase chain reaction, and cDNA sequencing. CF1 ATPase activities of the soluble enzymes were measured in the presence and absence of dithiothreitol (DTT). Mutant CF1 enzymes showed no effect of DTT although increased activity was observed for the wild-type enzyme. In vitro, phenazine methosulfate-dependent photophosphorylation assays revealed that wild-type CF1 exhibits a 2-fold stimulation in the presence of 25 mM DTT, whereas each of the mutant enzymes has activities that are DTT-independent. Growth measurements indicated that despite the absence of a regulatory disulfide/dithiol, the mutant strains grew with the same kinetics as wild type. This study provides evidence to illustrate the involvement of the gamma-subunit in the redox regulation of ATP synthesis in vivo. This work is also the first demonstration in C. reinhardtii of stable nuclear transformation using mutated genes to complement a known defect.

Animals↗

PubMed1995

The application of prostaglandin E1 indirect portal vein angiography and color Doppler ultrasound in patients with post-devascularization portal hypertension.

The selection of proper treatment is based on identification of the causes of massive hemorrhage of gastrointestinal tract after pericardial devascularization. The combined use of prostaglandin E1 indirect portal vein angiography, DSA of celiac artery and color Doppler can provide detailed information about portal vein system, including the presence of embolism, spongioid changes and devascularization of left gastric vein and left gastric artery and the direction of blood flow. If these techniques failed to reveal the causes of digestive tract bleeding, the endoscopy may show lesions of gastric mucosa, which could be accountable for the bleeding.

Adolescent↗

PubMed1989

Study on the mechanism of interferon action (XI)--Effect of pppA2'p5'A on the level of cAMP and cGMP in macrophages.

In this paper, the increase of cellular cAMP and cGMP levels in macrophages induced by ppA2'p5' A2'p5'A (briefly 2'-5'P3A3) is first reported. The optimal concentration of 2'-5' P3A3 for the elevation of cellular cGMP to the highest level is 10(-7)-10(-6) mol/L, while that for cAMP is 10(-7) mol/L. The time for cGMP to reach its peak value is 15 min and that for cAMP is 2 h, when the cells are treated with 2'-5' P3A3 at 10(-7) mol/L, which is the optimal concentration for developing biological effect of macrophages (phagocytosis). These results suggest that cGMP and cAMP may be related to, or may be the mediators for, 2'-5'P3A3 action.

Adenine Nucleotides↗

PubMed1989

[Dietary survey and biochemical study of blood and urine among Yi and Han nationality farmers in low prevalent district of hypertension].

This paper reports the dietary investigation (55 persons) and nutrient biochemical analysis of blood and urine (173 persons) among Yi and Han nationality farmers with low incidence of hypertension in Weinin, Guizhou. The results suggest that the three main nutrients as protein, fat and carbohydrate had no uniform relationship to the blood pressure, but high potassium and low sodium diet was intimately correlated to the low incidence of hypertension. The Na/K ratio of dietary intake and urine was more closely related to blood pressure. The relationship between calcium and blood pressure was quite complicated. The appropriate ratio of calcium and magnesium intake may be significant in the prevention and treatment of hypertension. It also indicates some intrinsic connection between lipid metabolism and blood pressure, while the degree of smoking is definitely correlated to blood pressure.

Adult↗