Biomedical subjects

Y Han

Publications and source records attributed to Y Han.

At least 217 records · Page 12Linked to original sources

PubMed1998

[Study of photoreflectance in Cd1-xMnxTe/Cd1-yMnyTe superlattices of II - VI diluted magnetic semiconductors].

The observation of photoreflectance spectra of Cd1-xMnxTe/Cd1-yMnyTe superlattices was carried out at temperature T = 80K. The samples were grown by molecular beam epitaxy (MBE) technique. The heavy-and light-hole excitonic transition structures 11H, 22H, 33H and 11L were observed and the theoretical calculations, including the strain effects, were performed. By comparison, both agree well.

English Abstract↗

PubMed1998

Functional homodimeric glycoprotein hormones: implications for hormone action and evolution

Background:. Human chorionic gonadotropin (hCG), lutropin, follitropin, and thyrotropin act as alphabeta heterodimers to control reproduction and thyroid function. The alpha and beta subunits of these proteins are divided into three loops (alpha1, alpha2,alpha3; beta1,beta2,beta3) by cysteine knots and the heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha2 like a seatbelt. Understanding how these hormones interact with their receptors, a matter of considerable dispute, would facilitate design of pro- and anti-fertility agents. Results:. By swapping alpha2 for beta2 and vice versa and, in some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared homodimeric analogs that have the conformation found in each 'half' of hCG. Homodimers containing loops beta1,alpha2,beta3 and none, part, or all of the seatbelt stimulated signal transduction to the same extent as hCG, albeit with lower potency. Those containing alpha1,beta2,alpha3 were inactive. Conclusions:. The activities of homodimers containing the beta1,alpha2,beta3 groove exceed those of other minimized analogs more than 100-1000-fold, suggesting this portion of the hormone forms the major receptor contact. The discovery that glycoprotein hormone heterodimers can be converted to functional homodimers supports the proposal that this protein family evolved from an active homodimeric ancestor by gene duplication and acquisition of mutations to loop 2 that prevent homodimerization. This approach to protein minimization should be applicable to other proteins composed of architecturally related subunits, including those that might have arisen by gene duplication.

Journal Article↗

PubMed1998

Functional homodimeric glycoprotein hormones: implications for hormone action and evolution.

BACKGROUND: Human chorionic gonadotropin (hCG), lutropin, follitropin, and thyrotropin act as alpha beta heterodimers to control reproduction and thyroid function. The alpha and beta subunits of these proteins are divided into three loops (alpha 1,alpha 2,alpha 3; beta 1,beta 2,beta 3) by cysteine knots and the heterodimer is stabilized by 20 beta-subunit residues wrapped around alpha 2 like a seatbelt. Understanding how these hormones interact with their receptors, a matter of considerable dispute, would facilitate design of pro- and anti-fertility agents. RESULTS: By swapping alpha 2 for beta 2 and vice versa and, in some cases, adding an amino-terminal coiled-coil dimerization domain, we prepared homodimeric analogs that have the conformation found in each 'half' of hCG. Homodimers containing loops beta 1,alpha 2,beta 3 and none, part, or all of the seatbelt stimulated signal transduction to the same extent as hCG, albeit with lower potency. Those containing alpha 1,beta 2,alpha 3 were inactive. CONCLUSIONS: The activities of homodimers containing the beta 1,alpha 2,beta 3 groove exceed those of other minimized analogs more than 100-1000-fold, suggesting this portion of the hormone forms the major receptor contact. The discovery that glycoprotein hormone heterodimers can be converted to functional homodimers supports the proposal that this protein family evolved from an active homodimeric ancestor by gene duplication and acquisition of mutations to loop 2 that prevent homodimerization. This approach to protein minimization should be applicable to other proteins composed of architecturally related subunits, including those that might have arisen by gene duplication.

Amino Acid Sequence↗

PubMed1997

Partition of transient and sustained inhibitory glycinergic input to retinal ganglion cells.

Physiological and pharmacological properties of possible subtypes of the native glycine receptor were investigated in retinal neurons using whole-cell voltage-clamp techniques. Two discrete inhibitory glycine responses were identified in ganglion cells. The responses could be distinguished pharmacologically: one was sensitive to strychnine and the other to 5,7-dichlorokynurenic acid. The two responses had different kinetics: the former had a fast onset and fast desensitization, whereas the latter had a slower onset and was much more sustained. The physiological and pharmacological distinctions suggest that the responses are mediated by different receptors. These receptors transduce glycinergic synaptic signals to ganglion cells, where they serve as low- and high-pass filters, respectively, of EPSPs.

Alanine↗

PubMed1997

Mechanism for biphasic rel A. NF-kappaB1 nuclear translocation in tumor necrosis factor alpha-stimulated hepatocytes.

The proinflammatory cytokine, tumor necrosis factor alpha (TNFalpha), is a potent activator of angiotensinogen gene transcription in hepatocytes by activation of latent nuclear factor-kappaB (NF-kappaB) DNA binding activity. In this study, we examine the kinetics of TNFalpha-activated translocation of the 65-kDa (Rel A) and 50-kDa (NF-kappaB1) NF-kappaB subunits mediated by inhibitor (IkappaB) proteolysis in HepG2 hepatoblastoma cells. HepG2 cells express the IkappaB members IkappaBalpha, IkappaBbeta, and IkappaBgamma. In response to TNFalpha, Rel A.NF-kappaB1 translocation and DNA binding activity follows a biphasic profile, with an "early" induction (15-30 min), followed by a nadir to control levels at 60 min, and a "late" induction (>120 min). The early phase of Rel A.NF-kappaB1 translocation depends on simultaneous proteolysis of both IkappaBalpha and IkappaBbeta isoforms; IkappaBgamma is inert to TNFalpha treatment. The 60-min nadir is due to a rapid IkappaBalpha resynthesis that reassociates with Rel A and completely inhibits its DNA binding activity; the 60-min nadir is not observed when IkappaBalpha resynthesis is prevented by cycloheximide treatment. By contrast, selective inhibition of IkappaBbeta proteolysis by pretreatment of HepG2 cells with the peptide aldehyde N-acetyl-Leu-Leu-norleucinal completely blocks the late phase of Rel A.NF-kappaB1 translocation. These studies indicate the presence of inducible and constitutive cytoplasmic NF-kappaB pools in hepatocytes. TNFalpha induces a coordinated proteolysis and resynthesis of IkappaB isoforms to produce dynamic changes in NF-kappaB nuclear abundance.

Cell Nucleus↗

PubMed1997

TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.

Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and IFN-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mRNA accumulation in human astroglioma and fibrosarcoma cell lines, but TGF-beta does not destabilize the CIITA message, suggesting an effect at the transcriptional level. In cells that stably overexpressed CIITA, leading to a constitutive class II MHC-positive phenotype, the inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell lines that possessed defects in TGF-beta signaling also became refractory to inhibition of IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF-beta suppresses IFN-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA.

Astrocytoma↗

PubMed1997

Influence of subunit interactions on lutropin specificity. Implications for studies of glycoprotein hormone function.

Bovine lutropin (bLH) and human chorionic gonadotropin (hCG) are heterodimeric glycoprotein hormones required for reproduction. Both bind rat LH receptors (rLHRs), but hCG binds human LH receptors (hLHRs) 1000-10,000 fold better than bLH. We tested the premise that this difference in affinity could be used to identify lutropin receptor contacts. Heterodimers containing hCG/bLH alpha- or beta-subunit chimeras that bound hLHR like hCG (or bLH) were expected to have hCG (or bLH) residues at the receptor contact sites. Analogs containing one subunit derived from hCG bound hLHR much more like hCG than bLH, indicating that each bLH subunit contains all the residues sufficient for high affinity hLHR binding. Indeed, the presence of bovine alpha-subunit residues increased the activities of some hCG analogs. The low hLHR activity of bLH was due primarily to an interaction between its alpha-subunit and beta-subunit residue Leu95. Leu95 does not appear to contact the hLHR since it did not influence the hLHR activity of heterodimers containing human alpha-subunit. These observations show that interactions within and between the subunits can significantly influence the activities of lutropins, thereby confounding efforts to identify ligand residues that contact these receptors.

Amino Acid Sequence↗

PubMed1997

Analysis of toxic drugs by capillary electrophoresis using polyacrylamide-coated columns.

Toxic drugs, including barbiturates and benzodiazepines, were analyzed using polyacrylamide-coated columns in capillary electrophoresis (CE). The separations were carried out in absence of electroosmotic flow. Seven kinds of barbiturates were successfully separated with the coated columns in free solution without further additives. Benzodiazepines, the electrically neutral solutes were introduced onto the coated column, and separated in presence of sodium dodecyl sulfate above its critical micelle concentration in the running buffer. This CE method offered fast and efficient separation of more hydrophobic solutes, such as benzodiazepines. The separation of seven barbiturates was studied in linear (noncross-linked) polyacrylamide solutions and in acrylamide/N-isopropylacrylamide (AA/IPAA) copolymer solutions to explore the effect of isopropyl groups in the AA/IPAA copolymer chain.

Acrylic Resins↗

PubMed1997

Effects of eye muscle proprioceptive activation on eye position in normal and exotropic subjects.

BACKGROUND: Activation of muscle spindles by vibration of eye muscles is known to induce illusory movements of fixated targets, but the effects on eye position have not been studied, either in normal subjects or in patients with exotropia. METHODS: Eye position was recorded from the covered, non-dominant eye with an infrared system in 11 subjects with normal eyes and binocular vision and in 10 patients with exotropia and abnormal binocular function. Activation of eye muscle spindles was done by vibration at 70 Hz of the inferior and lateral rectus muscles of the dominant eye, fixating a light-emitting diode in subdued light. RESULTS: Vibratory activation of proprioceptors in the inferior rectus muscle induced an eye movement mainly directed upward in both normal and exotropic subjects. The magnitude of the movement was on average 2.7 deg in normals and 2.4 deg in exotropes. Lateral rectus vibration induced a movement that was mainly temporally directed (abduction) of an average 2.1 deg in normal subjects, but a nasally directed (adduction) movement of 4.2 deg in exotropic subjects. In normal subjects the eye movement is of the same direction as the earlier reported visual illusory movements induced by the same type of proprioceptive activation, but in exotropic subjects the movements is in the opposite direction. CONCLUSIONS: Proprioceptive activation of eye muscles affects eye position, and the results also indicate that signals from eye muscles are processed differently in normals and strabismics, probably depending on the level of binocular function.

Adult↗

PubMed1997

Assessment of a mouse model of neutropenia and the effect of an anti-candidiasis monoclonal antibody in these animals.

As previously reported, monoclonal antibody (MAb) B6.1 increases resistance to hematogenous disseminated candidiasis in normal and SCID mice. In this study, MAb B6.1 was examined in a mouse model of neutropenia. The neutropenia was induced for a short period of time by a single dose of the anti-neutrophil antibody, MAb RB6-8C5, or for a protracted period by doses of MAb RB6-8C5 every other day. At low doses (< or = 25 microg/mouse), neutrophils were primarily affected, but at high doses (> or = 50 microg/mouse), lymphocytes were also depleted. Mice given either single or multiple doses of MAb RB6-8C5 were more resistant to experimental hematogenous disseminated candidiasis if they received MAb B6.1 before and after challenge with Candida albicans yeast cells intravenously. These results show the utility of MAb RB6-8C5 for induction of a protracted neutropenia in mice and demonstrate that MAb B6.1 can enhance resistance against candidiasis under neutropenic conditions.

Animals↗

PubMed1997

Overexpression of cellular glutathione peroxidase does not affect expression of plasma glutathione peroxidase or phospholipid hydroperoxide glutathione peroxidase in mice offered diets adequate or deficient in selenium.

Selenium-dependent cellular glutathione peroxidase (GPX1) overexpressing [GPX1(+)] mice were derived by microinjecting a 5.3-kb cloned entire mouse GPX1 genomic DNA into fertilized eggs. The objective of this study was to determine the effect of GPX1 overexpression and dietary selenium on the expression of selenoperoxidases and the status of lipid peroxidation of these transgenic animals. An experiment with a 2 x 2 factorial arrangement of treatments with 15 GPX1(+) and 15 control mice (2 mo old) was conducted for 8 wk. Ten mice of each group (half males and females) were fed a Se-deficient, Torula yeast basal diet (0.02 mg Se/kg, no supplemental vitamin E) and five mice (three males and two females) were fed the basal diet supplemented with 0.51 mg Se/kg as Na2SeO3. The GPX1(+) mice had greater GPX1 activities (one- to sixfold, P < 0.0001) than the control mice at both levels of dietary selenium in all tissues except for liver, in which such difference (100%, P < 0.05) was observed only in Se-deficient mice. The GPX1 mRNA level in kidney and in lung of the Se-deficient GPX1(+) mice was 81% and 7.5-fold greater (P < 0.003) than the respective control level. Overexpression of GPX1 did not alter phospholipid hydroperoxide glutathione peroxidase (GPX4) activities and mRNA levels or glutathione S-transferase (GST) activities in most of the tissues, plasma glutathione peroxidase (GPX3) activity or plasma Se concentrations. No differences in lipid peroxidation in kidney, lung or intestine were observed between the Se-deficient GPX1(+) and control mice. In conclusion, the overexpression of the GPX1 gene in these mice was tissue specific and did not affect the expression of GPX3, GPX4 or GST and plasma Se levels; dietary Se appeared to affect the GPX1 overexpression at its mRNA level.

Animals↗

PubMed1997

Protein and amino acid quality of meat and bone meal.

The in vivo protein quality of 14 meat and bone meals (MBM) was evaluated in three chick growth assays and a 48-h excreta collection assay using conventional and cecectomized roosters. In addition, in vitro evaluation of protein quality was assessed using pepsin N digestibility (0.2, 0.002, or 0.0002% pepsin), KOH protein solubility, and multi-enzyme pH change. Crude protein, lysine, and SAA in the MBM varied from 48 to 56, 2.32 to 3.01, and 1.0 to 2.13%, respectively. Protein efficiency ratio (weight gain:protein intake) estimated from feeding chicks diets containing 9% protein from a MBM ranged from 0.61 to 2.89 and averaged 1.78. Lysine bioavailability determined by slope-ratio chick assay ranged from 43 to 89%. True amino acid digestibility and TMEn values determined in cecectomized roosters were generally lower (P < 0.05) than those determined in conventional roosters. True digestibility of amino acids (percentage) also varied among MBM, with the mean (and range) for lysine, methionine, and cystine in cecectomized birds being 81 (73 to 88), 85 (77 to 91), and 58% (37 to 72%), respectively. Pepsin N digestibility values determined using 0.002 or 0.0002% pepsin were positively correlated (P < 0.05) with lysine digestibility. Pepsin N digestibility determined using 0.2% pepsin, KOH protein solubility, and multi-enzyme pH change were not significantly correlated with in vivo protein quality. Ash content was negatively correlated (-0.80, P < 0.05) with protein efficiency ratio. These results indicated that there is substantial variation in protein quality among commercial MBM and that pepsin N digestibility and ash content are correlated with some in vivo protein quality measurements.

Amino Acids↗

PubMed1997

Biochemical characterization of Candida albicans epitopes that can elicit protective and nonprotective antibodies.

We previously reported that the immunoglobulin M (IgM) monoclonal antibody (MAb) B6.1 protects mice against disseminated candidiasis, whereas the IgM MAb B6 does not. Both MAbs are specific for an adhesin fraction isolated from the cell surface of Candida albicans, but their epitope specificities differ. In the present study, we examined the surface locations of both epitopes and obtained structural information regarding the B6.1 epitope. Immunofluorescence confocal microscopic analysis of C. albicans yeast forms showed that epitope B6.1 is displayed rather homogeneously over the entire cell surface, whereas epitope B6 appears to have a patchy distribution. Both antibodies were essentially nonreactive with the surfaces of mycelial forms of the fungus, indicating that neither epitope is expressed on the surfaces of these forms. For isolation of the B6.1 epitope, the adhesin fraction consisting of cell surface phosphomannan was subjected to mildly acidic (10 mM HCl) hydrolysis and was fractionated into acid-labile and acid-stable portions by size exclusion chromatography. Antibody blocking experiments showed that the B6.1 epitope is an acid-labile moiety of the phosphomannan and that the B6 epitope is located in the acid-stable fraction. The B6 epitope appeared to be mannan because it was stable to heat (boiling) and protease treatments but was destroyed by alpha-mannosidase digestion. The B6.1 epitope eluted from the size exclusion column in two fractions. Mass spectroscopic analyses showed that one fraction contained material with the size of a mannotriose and that the other was a mixture of mannotriose- and mannotetraose-size substances. Dose response inhibition tests of the fractions indicated that the B6.1 epitope is associated with the mannotriose. Nuclear magnetic resonance (NMR) spectroscopic analysis of the epitope yielded data consistent with a beta-(1-->2)-linked mannotriose. The fine structure of the B6 epitope is under investigation. Information derived from these investigations will be useful both in understanding protective versus nonprotective antibody responses to C. albicans and in improving anti-Candida vaccine formulations.

Agglutination Tests↗

PubMed1997

Ionic basis of learning-correlated excitability changes in Hermissenda type A photoreceptors.

Repeated pairings of light and rotation (conditioning) result in persistent changes in excitability of Hermissenda type B and A photoreceptors, which are correlated with pairing-specific reductions in phototactic behavior. Although considerable attention has been devoted to characterization of conditioning-produced neurophysiological changes that occur in type B cells, less information is available concerning the changes produced in type A cells. Here we recorded from identified, synaptically isolated lateral and medial type A photoreceptors from conditioned, random-control, or untrained animals on retention days following conditioning. Type A photoreceptors from conditioned animals responded to light with a receptor potential that was significantly smaller than those of random-control or untrained animals, which did not differ. The phototactic suppression and type A cell light response magnitudes were negatively correlated for individual conditioned animals. Animals exhibiting strong phototactic suppression also showed small light responses. Expression of the training-associated light response difference was a calcium-dependent phenomenon: reducing extracellular calcium to < 1 microM enhanced the generator potential of A cells, regardless of conditioning history, and greatly reduced the differences in generator potential amplitude attributable to training. Voltage-clamp studies revealed that conditioning resulted in a two- to threefold increase in the amplitude of a voltage-dependent, sustained outward K+ current (I(Delayed)). I(Delayed) magnitudes were positively correlated with phototactic suppression for individual conditioned animals: type A cells of animals exhibiting strong phototactic suppression expressed large values of I(Delayed). I(Delayed) is a composite current, consisting of at least three separable components: 1) residual A current (I(A)); 2) slow, tetraethylammonium-sensitive calcium-activated K+ current (I(K-Ca)); and 3) a delayed-rectifier-type, voltage-dependent K+ current (I(K,v)). Analysis of these currents failed to reveal significant training-associated changes in I(A) or I(K-Ca). But I(K,v) was enhanced by approximately 60-150% in both lateral and medial cells and thus contributes to the conditioning-associated increase in I(Delayed).

Analysis of Variance↗

PubMed1997

Growth hormone-induced tyrosyl phosphorylation and deoxyribonucleic acid binding activity of Stat5A and Stat5B.

GH is known to activate JAK2 tyrosine kinase and members of the Stat family of transcription factors, including Stats 1, 3, and 5. The recent observation that at least two Stat5 proteins (Stat5A and Stat5B) exist in mouse and human, raises the question of whether GH activates both Stat5A and Stat5B and, if so, whether the requirements for activation are the same. An initial report investigating this issue demonstrated GH-dependent activation of Stat5A but not Stat5B. In this paper, we demonstrate (in COS cells expressing rat GH receptor (rGHR) and either Stat5A or Stat5B, 3T3-F442A fibroblasts, and CHO cells expressing rGHR) that GH induces tyrosyl phosphorylation of both Stat5A and Stat5B. Similar time courses of phosphorylation were observed for the two proteins. Interestingly, the pattern of observed bands differs for the two forms of Stat5. Two closely migrating Stat5A bands can be detected in cells treated with or without GH. Both of these bands become tyrosyl phosphorylated in response to GH. Three species of Stat5B are observed in untreated cells. An additional, more slowly migrating Stat5B band, appears upon treatment with GH. The three more slower migrating Stat5B bands observed in response to GH contain phosphorylated tyrosyl residues. We further demonstrate that GH induces binding of Stat5A and Stat5B, as well as Stat1, to the GAS-like element in the beta-casein promoter. We and others have demonstrated previously that specific regions of GHR are required for GH-dependent activation of what is here identified as Stat5B. To gain insight into the mechanism by which GH promotes tyrosyl phosphorylation of Stat5A, GH-dependent tyrosyl phosphorylation of Stat5A was examined in CHO cells expressing truncated and mutated rGHR. The results indicate that Stat5A and Stat5B require the same regions of rGHR for maximal activation by GH: the C-terminal half of the cytoplasmic domain; tyrosines 333 and/or 338 in the N-terminal half of the cytoplasmic domain; and the regions required for JAK2 activation. To dissect further the mechanism by which GH activates Stat5A and B, the requirement for JAK2 in GH-dependent Stat5 tyrosyl phosphorylation was assessed using JAK2-deficient cells expressing GHR (gamma2A-GHR) and the wild-type parental cell line expressing GHR (2C4-GHR). GH-induced tyrosyl phosphorylation of Stat5B in 2C4-GHR cells but not in the JAK2 deficient, gamma2A-GHR cells, indicating that JAK2 is required for GH-dependent tyrosyl phosphorylation of Stat5B. Western blotting revealed that Stat5A is not expressed in this cell type. Taken together, these findings suggest that: 1) GH activates both Stat5A and Stat5B in several cell types; 2) the pattern of bands observed differs for Stat5A and Stat5B; 3) GH-dependent tyrosyl phosphorylation of Stat5A requires specific regions of GHR, and these requirements are the same as for Stat5B; and 4) JAK2 kinase is required for GH-dependent tyrosyl phosphorylation of Stat5B and, most likely, Stat5A.

Animals↗

PubMed1997

JAK2 and STAT5, but not JAK1 and STAT1, are required for prolactin-induced beta-lactoglobulin transcription.

Several different Janus kinases (JAKs) and signal transducers and activation of transcription (STATs) have been implicated in mediating the biological responses induced by PRL, based on their ligand-dependent tyrosine phosphorylation and activation. However, these criteria alone do not prove that a particular JAK or STAT is essential for signal transduction. We have used mutant cell lines defective in JAK1, JAK2, or STAT1 to examine their roles in PRL-dependent signaling. JAK2 is absolutely required for PRL-dependent phosphorylation of the receptor, activation of STATs, and induction of beta-lactoglobulin. Wild type, but not kinase-negative JAK2, restores all responses to PRL in JAK2-defective cells, suggesting that JAK2 function, not merely the protein, is required. In contrast, JAK1, which is phosphorylated in response to PRL, is not required for any of these functions. Although STAT1 homodimers do form in response to PRL, no defect in PRL-dependent signaling is apparent when STAT1 is missing, suggesting that STAT5, which is strongly activated in response to PRL, is primarily responsible for driving the expression of PRL-responsive genes.

Animals↗

PubMed1997

Cathepsin B and middle cerebral artery occlusion in the rat.

Lysosomal proteases, although tightly regulated under physiological conditions, are known to contribute to cell injury after various forms of tissue ischemia have occurred. Because cathepsin B is a prominent lysosomal protease found in brain parenchyma, the authors hypothesized that it may contribute to neuronal cell death after focal cerebral ischemia. The authors measured the expression and spatial distribution of cathepsin B within the ischemic brain in 43 animals by means of immunohistochemical analysis in a rat model of transient middle cerebral artery (MCA) occlusion. Cathepsin B activity was also measured within specific ischemic brain regions by using an in vitro assay (22 animals). In addition, the authors tested the therapeutic effect of preischemic intraventricular administration of stefin A, a cysteine protease inhibitor, on the volume of cerebral infarction after transient MCA occlusion (15 animals). Increased cathepsin B immunoreactivity was detected exclusively within the ischemic neurons after 2 hours of reperfusion following a 2-hour MCA occlusion. Cathepsin B immunolocalization in the ischemic region decreased by 24 hours of reperfusion, but then increased by 48 hours of reperfusion because the infarct was infiltrated by inflammatory cells. Increased immunolocalization of cathepsin B in the inflammatory cells located in the necrotic infarct core continued through 7 days of reperfusion. Cathepsin B enzymatic activity was significantly increased in the ischemic tissue at 2, 8, and 48 hours, but not at 24 hours of reperfusion after 2 hours of MCA occlusion. Continuous intraventricular infusion of stefin A, before 2 hours of MCA occlusion (15 animals), significantly reduced infarct volume compared with control animals (12 animals): the percentage of hemispheric infarct volume was 20+/-3.9 compared with 33+/-3.5 (standard error of the mean; p = 0.025). These data indicate that neuronal cathepsin B undergoes increased expression and activation within 2 hours of reperfusion after a 2-hour MCA occlusion and may be a mechanism contributing to neuronal cell death. Intraventricular infusion of stefin A, an inhibitor of cathepsin B, significantly reduces cerebral infarct volume in rats.

Animals↗

PubMed1997

[The protective effect of SOD on injury of bone marrow hematopoietic progenitor cells of mice under 4 degrees C storage].

The protective effect of Cu, Zn, SOD on bone marrow hematopoietic progenitor cells of mice, under 4 degrees C storage was studied. The results showed, if 1.65 U or 0.165 U/ml SOD was added to the cell suspension for 3 days at 4 degrees C, the production rate of CFU-GM, CFU-E, BFU-E, CFU-Meg and CFU-Mix were 6.2, 2.6, 2.9, 4.0 and 5.1 times that of control group (without SOD) respectively. The survival rate of hematopoietic progenitor cells increased obviously. The mechanism of SOD effect is supposed to prevent hematopoietic progenitor cells from death, instead of the regulating proliferation. It may be closely related to the antioxidation of SOD which scavenges the superoxide free radicals.

Animals↗