Biomedical subjects

Xiaoping Zhu

Publications and source records attributed to Xiaoping Zhu.

25 records · Page 2Linked to original sources

PubMed2002

Role of nitric oxide in isometric contraction properties of rat diaphragm during hypoxia.

Hypoxia disturbs Ca(2+) regulation and increases the intracellular Ca(2+) concentration ([Ca(2+)](i)), which may in turn activate the nitric oxide synthase (NOS) regulated by [Ca(2+)](i). Since nitric oxide (NO) reduces the isometric contractility of rat diaphragm in vitro, we hypothesized that NO contributes to the impaired force generation of an hypoxic diaphragm. The effects of different concentrations of the NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), the NO scavenger haemoglobin (150 micro mol.l(-1)) and the NO donor spermine NONOate (Sp-NO; 1 mmol.l(-1)) were determined on isometric contractility during hypoxia [partial pressure of oxygen, PO(2), about 7 kPa (about 54 mmHg)] and hyperoxia [ PO(2) about 83 kPa (about 639 mmHg)]. Hypoxia significantly reduced maximal twitch force ( F(t)), and submaximal tetanic force (30 Hz, F(30)) in all L-NMMA groups. A low concentration of L-NMMA (30 micromol.l(-1)) increased F(30) but a high concentration (1,000 micromol.l(-1)) reduced F(30) during hypoxia. The effects of L-NMMA on force generation were more pronounced during hypoxia compared to hyperoxia. Peak increases in F(30) and F(t) were observed at a concentration of 30 micromol.l(-1) L-NMMA during hypoxia, but with 10 micromol.l(-1) L-NMMA during hyperoxia. The same concentration of haemoglobin increased F(30) and F(t) less during hypoxia compared to hyperoxia. The Sp-NO reduced F(t), F(30) and maximal tetanic force (F(0)) during hypoxia; these effects were abolished in the presence of haemoglobin. The Sp-NO did not alter F(t), F(30) and F(0)during hyperoxia. We conclude that NO plays a more prominent role during hypoxia and that NO contributes to the depression of force generation in the hypoxic rat diaphragm in vitro. This change may be related to an elevated NO generation within the hypoxic diaphragm.

Animals↗

PubMed2002

The heavy chain of neonatal Fc receptor for IgG is sequestered in endoplasmic reticulum by forming oligomers in the absence of beta2-microglobulin association.

The heavy chain (HC) of the neonatal Fc receptor (FcRn) for IgG is non-convalently associated with beta(2)-microglobulin (beta(2)m). In beta(2)m(-/-) mice, FcRn functions are greatly impaired. We sought to determine how FcRn HC, particularly its structure and biogenesis, is affected by the absence of beta(2)m. Human FcRn HC, expressed from the beta(2)m-null cell line FO-1(FcRn), was present as a monomeric 45-kDa protein under reducing conditions but primarily as a 92-kDa oligomeric protein under non-reducing conditions. Two-dimensional electrophoresis and MS analysis showed that the 92-kDa protein was a dimer of the 45-kDa HC. Immunostaining showed that FcRn HC in FO-1(FcRn) was co-localized with the endoplasmic reticulum (ER) protein Bip/GRP78 but not with an endosome protein, EEA1. In contrast, FcRn HC in FO-1(FcRn+beta2m) was detected in both the ER and endosome. The dimeric HC in FcRn oligomers was free of beta(2)m association in FO-1(FcRn+beta2m). Mutation of non-paired cysteine residues at positions 48 and 251 within the human FcRn cDNA failed to eliminate the oligomers. The FcRn HC oligomers could be reduced by reconstitution of FO-1(FcRn) with beta(2)m or by balanced expression of FcRn HC with beta(2)m, or beta(2)m fused with a KDEL retention sequence. Similarly, the majority of FcRn HC isolated from neonatal beta(2)m(-/-) mice was in a dimeric form under non-reducing conditions. The amount of FcRn HC was significantly decreased in beta(2)m(-/-) mice and FO-1(FcRn). Furthermore, beta(2)m-free FcRn HC was sensitive to endoglycosidase digestion. These results indicate that FcRn HC alone can form disulphide-bonded oligomers in the ER, which may represent a misfolded protein. The beta(2)m association with FcRn HC is critical for correct folding of FcRn and exiting the ER for routing to endosomes and the cell surface.

Animals↗

PubMed2002

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia.

Nitric oxide (NO) is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (Po(2) approximately 7 kPa). l-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects of l-NMMA were prevented by coadministration with the NOS substrate l-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.

Animals↗

PubMed2002

A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans.

BACKGROUND: Integrins are heterodimeric (alphabeta) transmembrane receptors for extracellular matrix (ECM) ligands. Through interactions with molecular partners at cell junctions, they provide a connection between the ECM and the cytoskeleton and regulate many aspects of cell behavior. A number of integrin-associated molecules have been identified; however, in many cases, their function and role in the animal remain to be clarified. RESULTS: We have identified the Nck-interacting kinase (NIK), a member of the STE20/germinal center kinase (GCK) family, as a partner for the beta1A integrin cytoplasmic domain. We find that NIK is expressed in the nervous system and other tissues in mouse embryos and colocalizes with actin and beta1 integrin in cellular protrusions in transfected cells. To demonstrate the functional significance of this interaction, we used Caenorhabditis elegans, since it has only one beta (PAT-3) integrin chain, two alpha (INA-1 and PAT-2) integrin chains, and a well-conserved NIK ortholog (MIG-15). Using three methods, we show that reducing mig-15 activity results in premature branching of commissures. A significant aggravation of this defect is observed when mig-15 activity is compromised in a weak ina-1 background. Neuronal-specific RNA interference against mig-15 or pat-3 leads to similar axonal defects, thus showing that both mig-15 and pat-3 act cell autonomously in neurons. Finally, we show a genetic interaction between mig-15, ina-1, and genes that encode Rac GTPases. CONCLUSIONS: Using several models, we provide the first evidence that the kinase NIK and integrins interact in vitro and in vivo. This interaction is required for proper axonal navigation in C. elegans.

Actins↗

PubMed2002

Comparison of automated and manual MRI volumetry of hippocampus in normal aging and dementia.

PURPOSE: To determine whether automatic and manual measurements of hippocampal volume differences on MRI between normal aging, cognitive impairment (CI), and Alzheimer's disease (AD) yield similar results. MATERIALS AND METHODS: Reliability was determined for an automatic and a manual method on nine volunteers (22-83 years old) who underwent MRI twice in 1 day. Hippocampal volumes of 20 cognitively normal subjects (mean age 74.0 +/- 6.2 years) and age-matched patients (20 CI and 20 AD) were compared. RESULTS: The intraclass correlation for automatic calculations of hippocampal volume was 0.94; for manual tracing it was 0.99. Volume differences between cognitively normal, CI, and AD subjects from the automatic and manual methods were similar. CONCLUSION: Because the automatic calculations were faster and less susceptible to rater bias than manual tracing, this automated method is expected to be very useful for analyzing hippocampal changes in studies of aging and dementia.

Adult↗

PubMed2002

[Application of meshed acellular dermis xenograft (pigskin) with scalp thin skin autograft in 15 patients].

OBJECTIVE: To present the clinical application of the meshed acellular dermis xenograft with scalp thin split-thickness skin autograft. METHODS: The meshed acellular dermis xenograft (pigskin) was placed on the granulation or defects after scar resection. Four or five days afterwards, scalp thin split-thickness skin was transplanted. A total of 15 patients with 25 wounds were treated using this technique. The survival rates and quality of the grafts were observed. RESULTS: The survival rate of the meshed acellular dermis xenograft was (96.40 +/- 2.60)% and the scalp thin split-thickness skin autograft was (97.44 +/- 3.50)%. All grafts showed normal skin-alike color and elastic and smooth texture. CONCLUSION: The combined use of meshed acellular dermis xenograft and scalp skin autograft demonstrated an ideal way for the repair of full-thickness skin burn or defects from scar resection. The scalp can provide thin skin graft repeatedly without influence of the hair.

Adolescent↗

PubMedDate not supplied

Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging.

Previous magnetic resonance (MR) spectroscopy studies of Alzheimer disease (AD) reporting reduced N-acetyl aspartate (NAA) and increased myo-Inositol (mI) used single voxel techniques, which have limited ability to assess the regional distribution of the metabolite abnormalities. The objective of this study was to determine the regional distribution of NAA and mI alterations in AD by using MR spectroscopic imaging. Fourteen patients with AD and 22 cognitively normal elderly were studied using structural MR imaging and MR spectroscopic imaging. Changes of NAA, mI, and various metabolite ratios were measured in frontal and parietal lobe gray matter (GM) and white matter. This study found: (1) when compared with cognitively normal subjects, AD patients had increased mI and mI/creatine (Cr) ratios primarily in parietal lobe GM, whereas frontal lobe GM and white matter were spared; (2) in the same region where mI was increased, AD patients had also decreased NAA and NAA/Cr ratios, replicating previous findings; (3) however, increased mI or mI/Cr ratios did not correlate with decreased NAA or NAA/Cr ratios; and (4) using mI/Cr and NAA/Cr together improved sensitivity and specificity to AD from control as compared with NAA/Cr alone. In conclusion, decreased NAA and increased mI in AD are primarily localized in parietal lobe GM regions. However, the NAA and mI changes are not correlated with each other, suggesting that they represent different processes that might help staging of AD.

Aged↗