Biomedical subjects

Q Jiang

Publications and source records attributed to Q Jiang.

At least 19 recordsLinked to original sources

PubMed1998

Cystic fibrosis transmembrane conductance regulator-associated ATP release is controlled by a chloride sensor.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis, and has also been closely associated with ATP permeability in cells. Using a Xenopus oocyte cRNA expression system, we have evaluated the molecular mechanisms that control CFTR-modulated ATP release. CFTR-modulated ATP release was dependent on both cAMP activation and a gradient change in the extracellular chloride concentration. Activation of ATP release occurred within a narrow concentration range of external Cl- that was similar to that reported in airway surface fluid. Mutagenesis of CFTR demonstrated that Cl- conductance and ATP release regulatory properties could be dissociated to different regions of the CFTR protein. Despite the lack of a need for Cl- conductance through CFTR to modulate ATP release, alterations in channel pore residues R347 and R334 caused changes in the relative ability of different halides to activate ATP efflux (wtCFTR, Cl >> Br; R347P, Cl >> Br; R347E, Br >> Cl; R334W, Cl = Br). We hypothesize that residues R347 and R334 may contribute a Cl- binding site within the CFTR channel pore that is necessary for activation of ATP efflux in response to increases of extracellular Cl-. In summary, these findings suggest a novel chloride sensor mechanism by which CFTR is capable of responding to changes in the extracellular chloride concentration by modulating the activity of an unidentified ATP efflux pathway. This pathway may play an important role in maintaining fluid and electrolyte balance in the airway through purinergic regulation of epithelial cells. Insight into these molecular mechanisms enhances our understanding of pathogenesis in the cystic fibrosis lung.

1-Methyl-3-isobutylxanthine↗

PubMed1998

Diffusion, perfusion, and T2 magnetic resonance imaging of anti-intercellular adhesion molecule 1 antibody treatment of transient middle cerebral artery occlusion in rat.

The effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody treatment of transient (2 h) middle cerebral artery (MCA) occlusion in the rat was measured using diffusion (DWI)-, T2 (T2I)- and perfusion (PWI)-weighted magnetic resonance imaging. Rats were treated upon reperfusion with an anti-ICAM-1 monoclonal antibody (n=11) or a control antibody (n=7). DWI, T2I and PWI were performed before, during, and after induction of focal cerebral ischemia from 1 h to 7 days. In both groups, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) values in the ischemic region significantly declined from the preischemic ADCw values (p<0. 05). The post ischemic increase in T2 of the control group was significantly higher at 48 h than in the anti-ICAM-1 treated group (p<0.05). CBF was not significantly different between the two groups. The temporal profiles of MRI cluster analysis, which combines ADCw and T2 maps into a single image, was significantly different between groups. These data suggest that the neuroprotective effect of anti-ICAM-1 antibody treatment is reflected in reductions of T2 and lesion growth during reperfusion and may not be associated with increased cerebral perfusion.

Animals↗

PubMed1998

Vector-specific complementation profiles of two independent primary defects in cystic fibrosis airways.

Cystic fibrosis (CF) lung disease has been linked to multiple primary defects in airway epithelia caused by a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR) gene. These defects include altered Cl- and Na+ permeability as well as intracellular defects in glycoprotein processing. This apparent diversity in CFTR function is reflected in the complex patterning of CFTR expression in airway epithelia. Such complexities present challenges in the design of CF gene therapies that are capable of reconstituting the endogenous patterns of CFTR gene expression in appropriate target cells. Using a human bronchial xenograft model of the CF airway, we have evaluated the efficacy of recombinant adenoviral and cationic liposome-mediated gene transfer to correct Cl- permeability and mucous sulfation defects found in CF lung disease. Results from these studies demonstrated a clear vector-specific complementation profile for these two defects that was dependent on the type of cell transduced and the level of transgene expression. Single-dose administration of recombinant adenovirus effectively transduced high levels of CFTR transgene expression in 11 +/- 1% of epithelial cells and was capable of correcting cAMP-induced changes in Cl- permeability to 91 +/- 14% that seen in non-CF airways. However, this level of transgene expression was incapable of reversing defects in mucous sulfation due to the lack of efficient targeting to goblet cells. In contrast, cationic liposome-mediated delivery of CFTR encoding plasmids to CF airways achieved extremely low levels of transgene expression with insignificant correction (7.4 +/- 2.4%) of cAMP-induced Cl- permeability. This low level of transgene expression, however, efficiently reduced mucous sulfation to levels seen in non-CF airways. Differences in the complementation profiles of these two vectors in correcting Cl- permeability and mucous sulfation defects mirror the ability of recombinant adenovirus and liposomes to reconstitute only certain features of the endogenous distribution and abundance of CFTR protein expression. Such findings suggest that the level of intracellular CFTR required to facilitate proper glycoprotein processing may be much lower than that needed to mediate bulk Cl- flow across the airway epithelium. In summary, these data present the first example by which two different vector systems can efficiently complement independent primary defects associated with a single dysfunctional gene.

Adenoviridae↗

PubMed1998

Identification of a novel mouse hepatic 52 kDa protein that interacts with the cAMP response element of the rat angiotensinogen gene.

To identify the nuclear protein(s) that interact with the putative cAMP response element (CRE) of the rat angiotensinogen (ANG) gene (i.e. nt 806-779 upstream of the transcriptional start site), mouse liver nuclear proteins were prepared for the present studies. The DNase 1 footprinting protection analysis revealed that nt -799/-788 in the 5'-flanking region of the rat ANG gene are protected by the mouse liver nuclear protein. Gel mobility-shift assays revealed that the addition of the unlabelled DNA fragment, ANG nt -806/-779 competed effectively with the binding of the labelled ANG nt -806/-779 to the mouse liver nuclear proteins but the addition of unlabelled mutants of ANG nt -806/-779 were only weakly effective in competing with the labelled ANG nt -806/-779. The addition of unlabelled CRE of the somatostatin (SOM) gene and the CRE of the tyrosine aminotransferase (TAT) gene was also ineffective in competing with the labelled ANG nt -806/-779. Southwestern blot analysis revealed that the labelled ANG nt -806/-779 interacted with two mouse liver nuclear proteins with apparent molecular masses of 52 and 43 kDa, whereas the labelled SOM-CRE, TAT-CRE and the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene interacted with one molecular species of 43 kDa. The binding of the labelled ANG nt -806/-779 to the 52 kDa protein was effectively competed for by the addition of unlabelled ANG nt -806/-779 but not by unlabelled SOM-CRE, TAT-CRE and PEPCK-CRE. Finally, Western blot analysis revealed that polyclonal antibodies against the CRE-binding protein (CREB) interacted with the mouse liver nuclear 43 kDa protein but not with the 52 kDa protein. These studies demonstrate that the CRE of the rat ANG gene (ANG nt -806/-779) interacts with the 43 kDa CREB and a novel 52 kDa protein from mouse liver. The novel 52 kDa protein is immunologically distinct from the 43 kDa CREB. These studies suggest that the 52 kDa protein might have a role in the expression of the hepatic ANG gene.

Angiotensinogen↗

PubMed1998

Molecular dynamics simulation of a synthetic ion channel.

A molecular dynamics simulation has been performed on a synthetic membrane-spanning ion channel, consisting of four alpha-helical peptides, each of which is composed of the amino acids leucine (L) and serine (S), with the sequence Ac-(LSLLLSL)3-CONH2. This four-helix bundle has been shown experimentally to act as a proton-conducting channel in a membrane environment. In the present simulation, the channel was initially assembled as a parallel bundle in the octane portion of a phase-separated water/octane system, which provided a membrane-mimetic environment. An explicit reversible multiple-time-step integrator was used to generate a dynamical trajectory, a few nanoseconds in duration for this composite system on a parallel computer, under ambient conditions. After more than 1 ns, the four helices were found to adopt an associated dimer state with twofold symmetry, which evolved into a coiled-coil tetrameric structure with a left-handed twist. In the coiled-coil state, the polar serine side chains interact to form a layered structure with the core of the bundle filled with H2O. The dipoles of these H2O molecules tended to align opposite the net dipole of the peptide bundle. The calculated dipole relaxation function of the pore H2O molecules exhibits two reorientation times. One is approximately 3.2 ps, and the other is approximately 100 times longer. The diffusion coefficient of the pore H2O is about one-third of the bulk H2O value. The total dipole moment and the inertia tensor of the peptide bundle have been calculated and reveal slow (300 ps) collective oscillatory motions. Our results, which are based on a simple united atom force-field model, suggest that the function of this synthetic ion channel is likely inextricably coupled to its dynamical behavior.

Amino Acid Sequence↗

PubMed1998

Strain differences in adrenal microsomal steroid metabolism in guinea pigs.

We recently reported that CYP2D16, a xenobiotic-metabolizing P450 isozyme, was expressed at higher levels in adrenal microsomes from inbred Strain 13 guinea pigs than in those from outbred English Short Hair (ESH) animals. Studies were done to determine if there also were strain differences in adrenal microsomal steroid metabolism. In both inner (zona reticularis) and outer (zona fasciculata plus zona glomerulosa) zone preparations of the adrenal cortex, 21-hydroxylase activities were greater in microsomes from ESH than from Strain 13 guinea pigs. By contrast, 17alpha-hydroxylase activities were similar in the two strains. In both strains, 21-hydroxylase activities were greater in inner than outer zone microsomes, but the opposite was found for 17alpha-hydroxylase activities (outer>inner). Northern and Western analyses revealed higher levels of CYP21 mRNA and protein in adrenals from ESH than Strain 13 guinea pigs, but there were no strain differences in CYP17 mRNA or protein concentrations. Despite the zonal differences in adrenal 17alpha-hydroxylase and 21-hydroxylase activities, CYP17 and CYP21 mRNA and protein levels were similar in the inner and outer zones within each strain of guinea pig. The results demonstrate strain differences in microsomal steroid metabolism that are explained by differences in CYP21 expression. By contrast, the zonal differences in steroid hydroxylase activities may be attributable to post-translational mechanisms.

Adrenal Glands↗

PubMed1998

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis.

Cystic fibrosis (CF) has become a paradigm disorder for the clinical testing of gene therapies in the treatment of inherited disease. In recent years, efforts directed at gene therapy of CF have concentrated on improving gene delivery systems to the airway. Surrogate endpoints for complementation of CFTR dysfunction in the lung have been primarily dependent on correction of chloride transport abnormalities. However, it is now clear that the pathophysiology of CF airways disease is far more complex than can be solely attributed to altered chloride permeability. For example, in addition to functioning as a chloride channel, CFTR also has been implicated in the regulation of other apical membrane conductance pathways through interactions with the amiloride sensitive epithelial sodium channel (ENaC) and the outwardly rectifying chloride channel (ORCC). Superimposed on this functional diversity of CFTR is a highly regulated pattern of CFTR expression in the lung. This heterogeneity occurs at both the level of CFTR protein expression within different cell types in the airway and the anatomical location of these cells in the lung. Potential targets for gene therapy of CF include ciliated, non-ciliated, and goblet cells in the surface airway epithelium as well as submucosal glands within the interstitium of the airways. Each of these distinct cellular compartments may have functionally distinct roles in processes which affect the pathogenesis of CF airways disease, such as fluid and electrolyte balance. However, it is presently unclear which of these cellular targets are most pathophysiologic relevant with regard to gene therapy. Elucidation of the underlying mechanisms of CFTR function in the airway will allow for the rational design of gene therapy approaches for CF lung diseases. This review will provide a summary of the field's current knowledge regarding CFTR functional diversity in the airway and the implications of such diversity for gene therapies of CF lung disease.

Cystic Fibrosis↗

PubMed1998

Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat.

Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values (P < 0.001). However, mean CBF and ADCw in the rt-PA-treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T2 in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA-treated group (P < 0.05). Significant correlations (r > or = 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.

Animals↗

PubMed1998

Isolation and characterization of a group of oligopeptides related to oxidized glutathione from the root of Panax ginseng.

Six gamma-glutamyl oligopeptides were isolated for the first time from aqueous methanol extracts of Panax ginseng root by using column chromatography on ion-exchange resin, gel filtration and reverse-phase high-performance liquid chromatography. Their structures had been established with the methods of amino acid analysis, N-terminal, C-terminal determination and double-coupling sequence analysis. They were: P-I (N-gamma-glutamylcystinyl-bis-glycine), P-ll (gamma-glutamylcysteinylglycine disulfide, oxidized glutathione), P-III (N,N'-bis-gamma-glutamylcystinylglycine), P-IV (gamma-glutamylcysteinylglycinamide disulfide), P-V (N-gamma-glutamylglycylcysteine disulfide), P-VI(gammaglutamylarginine); five of them are related to oxidized glutathione. The structures were further confirmed by the chemical synthesis. As far as we know, P-V (N-gamma-glutamylglycylcysteine disulfide) is a new biologically active peptide which exhibits somnogenic effect and is more potent than that of P-II.

Amino Acids↗

PubMed1998

Genotypic characterization of clarithromycin-resistant and -susceptible Helicobacter pylori strains from the same patient demonstrates existence of two unrelated isolates.

Clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori isolates from the same patient were investigated for the mode of development and mechanism of clarithromycin resistance. The clarithromycin-resistant strain UA1182 harbors homozygous A-to-G mutations at position 2143 in both copies of the 23S rRNA gene and has a phenotype of resistance to clarithromycin and clindamycin but no significant resistance to streptogramin B. Pulsed-field gel electrophoresis patterns of NruI- and NotI-digested genomic DNA from the Clas and Clar isolates demonstrated that they are genetically distinct, suggesting that the development of clarithromycin resistance is not from the mutation of the existing Clas strain but from a completely new strain.

Anti-Bacterial Agents↗

PubMed1998

Epidemiological study and genetic analysis of GB virus C infection in general population from an area endemic for hepatitis C.

The aim of this work was to study the prevalence, potential risk factors, clinical and laboratory features of GB virus C (GBV-C) infection in general population from an area endemic for hepatitis C. A reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of GBV-C RNA was used to examine the prevalence of GBV-C RNA in both hepatitis C virus (HCV) endemic (R town) and nonendemic areas (M town) in Yamagata prefecture, Japan. In R town, GBV-C RNA was detected in 23 (2.9%) out of the 800 residents, whereas anti-HCV and HCV-RNA were found in 226 (28.3%) and 163 (20.4%), respectively. The prevalence of GBV-C RNA in R town (2.9%) was higher than that in M town (1.0%), although the difference was not statistically significant. The individuals with anti-HCV had significantly higher frequency of active GBV-C-infection than those without anti-HCV in both towns. No evidence indicating that GBV-C infection affected the severity of hepatitis C was obtained. The multivariate analysis revealed that the young anti-HCV positive individuals with a history of blood transfusion had higher incidence of active GBV-C infection. The phylogenetic analysis showed that the GBV-C isolates from both R and M towns were divided into two separate branch groups designated HG and Asia GB groups.

Adult↗

PubMed1997

Relative chlorinating, nitrating, and oxidizing capabilities of neutrophils determined with phagocytosable probes.

The capabilities of stimulated neutrophils to initiate intraphagosomal and extracellular chlorination, nitration, and other oxidative reactions has been evaluated using a fluorescent particle and soluble phenolic compounds as target molecules. Neutrophils activated by the soluble stimulus, phorbol myristate acetate, both chlorinated fluorescein that was covalently attached to polyacrylamide microspheres and initiated tyrosine dimerization. When nitrite ion was present at millimolar concentration levels in the medium, nitration of the phenolic rings also occurred; the relative extent of nitration increased as the nitrite concentration was increased. Myeloperoxidase (MPO) also catalyzed nitration and chlorination of fluorescein and the fluorescein-conjugated particles in cell-free solutions; the relative nitration yields increased with increasing [NO2-]/[Cl-] ratios. Nitration did not involve intermediary formation of nitrating agents derived from reaction between MPO-generated HOCl and NO2- because this reaction also occurred in chloride-free media and direct addition of HOCl to solutions containing NO2- and fluorescein gave only chlorinated products. In marked contrast to these extracellular reactions, intraphagosomal nitration of the fluorescein-conjugated particles could not be detected (even at [NO2-] as high as 0.1 M), whereas chlorination of the probe was extensive. These data indicate that intraphagosomal aromatic nitration in neutrophils is negligible, although extracellular nitration of phenolic compounds by secreted MPO could occur at physiological concentration levels of NO2-.

Catalysis↗

PubMed1997

Cloning and functional characterization of Helicobacter pylori fumarate reductase operon comprising three structural genes coding for subunits C, A and B.

In this study, we cloned and sequenced the Helicobacter pylori genes encoding fumarate reductase (FRD). H. pylori frdA, frdB and frdC specify polypeptides of 715, 245 and 254 aa, respectively. The deduced aa sequences of FrdA and FrdB are highly homologous to those of the corresponding subunits of Wolinella succinogenes FRD and also exhibit a significant sequence identity with other bacterial FRD and succinate dehydrogenase subunits A and B. However, H. pylori FrdC shares a striking degree of sequence identity only with W. succinogenes FrdC, which is a cytochrome b with two haem groups. The products encoded by H. pylori frdA, frdB and frdC were overproduced in maxicells and H. pylori FrdA was characterized using an anti-E. coli FrdA serum. H. pylori FRD activity, which was measured as fumarate-dependent benzyl viologen oxidation, is membrane-associated. Inactivation of frdA led to the loss of such activity and the mutant H. pylori cells were delayed (approx. 10-20 h behind their parent cells) in entering the mid-log phase, suggesting that FRD-driven metabolism plays an active but non-essential role for growth of H. pylori cells in vitro. H. pylori FRD contains three subunits, of which FrdA and FrdB appear to form the catalytic dimer, whereas FrdC serves as a membrane anchor.

Amino Acid Sequence↗

PubMed1997

A rat model of focal embolic cerebral ischemia.

We developed a new model of embolic cerebral ischemia in the rat which provides a reproducible and predictable infarct volume within the territory supplied by the middle cerebral artery (MCA). The MCA was occluded by an embolus in Wistar rats (n = 71). An additional three non-embolized rats were used as a control. Cerebral blood flow (CBF) was measured by means of laser Doppler flowmetry (LDF) and perfusion weighted imaging (PWI) before and after embolization. The evolution of the lesion was monitored by diffusion weighted imaging (DWI). Cerebral vascular perfusion patterns were examined using laser scanning confocal microscopy. Infarct volumes were measured on hematoxylin and eosin (H&E) stained coronal sections. The lodgment of the clot at the origin of the MCA and the ischemic cell damage were examined using light microscopy. Regional CBF in the ipsilateral parietal cortex decreased to 43 +/- 4.1% (P < 0.05) of preischemic levels (n = 10). Confocal microscopic examination revealed a reduction of cerebral plasma perfusion in the ipsilateral MCA territory (n = 6). MRI measurements showed a reduction in CBF and a hyperintensity DWI encompassing the territory supplied by the MCA (n = 4). An embolus was found in all rats at 24 h after embolization. The infarct volume as a percentage of the contralateral hemisphere was 32.5 +/- 3.31% at 24 h (n = 20), 33.0 +/- 3.6% at 48 h (n = 13), and 34.5 +/- 4.74% at 168 h (n = 12) after embolization. This model of embolic focal cerebral ischemia results in ischemic cell damage and provides a reproducible and predictable infarct volume. This model is relevant to thromboembolic stroke in humans and may be useful in documenting the safety and efficacy of fibrinolytic intervention and in investigating therapies complementary to antithrombotic therapy.

Animals↗

PubMed1997

Mutagenesis reveals structure-activity parallels between human A2A adenosine receptors and biogenic amine G protein-coupled receptors.

Structure-affinity relationships for ligand binding at the human A2A adenosine receptor have been probed using site-directed mutagenesis in the transmembrane helical domains (TMs). The mutant receptors were expressed in COS-7 cells and characterized by binding of the radioligands [3H]CGS21680, [3H]NECA, and [3H]XAC. Three residues, at positions essential for ligand binding in other G protein-coupled receptors, were individually mutated. The residue V(3.32) in the A2A receptor that is homologous to the essential aspartate residue of TM3 in the biogenic amine receptors, i.e., V84(3.32), may be substituted with L (present in the A3 receptor) but not with D (in biogenic amine receptors) or A. H250(6.52), homologous to the critical N507 of rat m3 muscarinic acetylcholine receptors, may be substituted with other aromatic residues or with N but not with A (Kim et al. J. Biol. Chem. 1995, 270, 13987-13997). H278(7.43), homologous to the covalent ligand anchor site in rhodopsin, may not be substituted with either A, K, or N. Both V84L(3.32) and H250N(6.52) mutant receptors were highly variable in their effect on ligand competition depending on the structural class of the ligand. Adenosine-5'-uronamide derivatives were more potent at the H250N(6.52) mutant receptor than at wild type receptors. Xanthines tended to be close in potency (H250N(6.52)) or less potent (V84L(3.32)) than at wild type receptors. The affinity of CGS21680 increased as the pH was lowered to 5.5 in both the wild type and H250N(6.52) mutant receptors. Thus, protonation of H250(6.52) is not involved in this pH dependence. These data are consistent with a molecular model predicting the proximity of bound agonist ligands to TM3, TM5, TM6, and TM7.

Adenosine↗

PubMed1997

Study on oxygen supply and protection of bone marrow in acute radiation injured mice.

After irradiated by 8 Gy 60Co gamma-ray, mice were intraperitoneally injected immediately with 0.2 ml 100% compound blood-activating soup twice a day for 10 days. The in situ ulnar bone marrow partial pressure of oxygen (PbO2) was determined in vivo before, during and after irradiation respectively. The bone marrow sections in the same part were observed. Our results showed that the normal murine ulnar PbO2 was 12.72 +/- 1.05 kPa. During irradiation, the level of PbO2 decreased to 10.78 +/- 1.17 kPa (P < 0.001). And 3 days after irradiation, PbO2 decreased to 9.75 +/- 0.52 kPa, suggesting that the commonly used "blood-activating and stasis-eliminating" Chinese drugs could promote the rehabilitation and proliferation of bone marrow microvessels in the acute radiation injured mice, expand their areas, increase the oxygen supply of bone marrow microenvironment, thereby leading to PbO2 much higher increase than that of control group. It is also helpful in the proliferation and rehabilitation of hematopoietic cells.

Animals↗

PubMed1997

The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat.

We have developed a multiparameter magnetic resonance imaging (MRI) cluster analysis model of acute ischemic stroke using T2 relaxation times and the diffusion coefficient of water (ADCw). To test the ability of this model to predict cerebral infarction, male Wistar rats (n = 7) were subjected to 2 h of transient middle cerebral artery (MCA) occlusion, and diffusion and T2 weighted MRI were performed on these rats before, during and up to 7 days after MCA occlusion. MRI tissue signatures, specified by values of ADCw and T2 were assigned to tissue histopathology. Significant correlations were obtained between MRI signatures at different time points and histopathologic measurements of lesion area obtained at 1 week. In addition, we compared the temporal evolution of MRI tissue signatures to a separate population of animals at which histological data were obtained at select times of reperfusion. A significant shift (p < or = 0.05) within signatures reflecting tissue histopathology was demonstrated as the ischemic lesion evolved over time. Our data suggest, that the MRI signatures are associated with the degree of ischemic cell damage. Thus, the tissue signature model may provide a noninvasive means to monitor the evolution of ischemic cell damage and to predict final outcome of ischemic cell damage.

Animals↗

PubMed1997

Further evaluation of the safety and protective efficacy of live attenuated hepatitis A vaccine (H2-strain) in humans.

A study on the possibility of transmission of live hepatitis A vaccine (H2-strain) from vaccinees to nonvaccinees was conducted. As a result, no seroconversion was found among 87 seronegative nonvaccinees, who had a close contact with their 141 subcutaneously vaccinated classmates nor was it found among 101 seronegative children administered the vaccine orally. The above fundings suggest that by losing the ability to be transmitted orally the vaccine virus may result in a decreasing possibility of dissemination among contacts. A 4-year study on the protective efficacy of the H2-strain vaccine was done at 11 primary schools starting at 1991 in Shaoxing County. Since then, there has been no hepatitis A reported among 18102 cumulative person-years in the vaccination group, while 495 cases occurred among 242168 cumulative person-years in the control groups. A large scale vaccination with a cumulative vaccination coverage of 89.45% was carried out in Jiaojiang City among children 1-15 years old. Hepatitis A in this age group in the city, which had 12-87 cases per annum with an average of 32 for 8 years before vaccination, decreased drastically to 0-1 cases after vaccination. The protective efficacy of H2-strain vaccine proved to be satisfactory.

Administration, Oral↗