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Aged↗
Biomedical subjects
S Takeda
Publications and source records attributed to S Takeda.
The crystal structure of troponin C in complex with N-terminal fragment of troponin I. The mechanism of how the inhibitory action of troponin I is released by Ca(2+)-binding to troponin C.
Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key role in Ca2+ dependent regulation of muscle contraction. To elucidate the interactions between the Tn subunits and the conformation of TnC in the Tn complex, we have determined the crystal structure of TnC in complex with the N-terminal fragment of TnI (TnI1-47). The structure was solved by single isomorphous replacement method in combination with multiple wavelength anomalous dispersion data. The refinement converged to a crystallographic R-factor of 22.2% (R-free = 32.6%). The central, connecting alpha-helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the center and bent by 90 degrees. As a result, the TnC in the complex has a compact globular shape with direct interactions between the N- and C-lobes, in contrast to the elongated dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha-helix stretches on the surface of TnC and stabilizes its compact conformation by multiple contacts with both TnC lobes. The amphiphilic C-terminal end of the TnI1-47 alpha-helix is tightly bound in the hydrophobic pocket of the TnC C-lobe through 38 van der Waals interactions. The results indicate the major difference between integrated (TnC) and isolated (calmodulin) Ca2+ receptors. The TnC/TnI1-47 structure suggests the model for a novel regulatory TnI segment bound to TnC and implies the mechanism of how Tn regulates the muscle contraction.
Animals↗
Adenosine 5'-triphosphate binding to bovine serum albumin.
Binding of ATP to bovine serum albumin was shown by ultrafiltration and NMR. The binding was pH dependent. Scatchard analysis revealed that at pH 5.4, 6.4 and 7.4, dissociation constant Kd was 13, 40 and 120 microM, respectively, and no binding was observed at pH 8.4. The binding stoichiometry was 1:1 for all pH. Dimer of BSA did not bind ATP. From chemical shifts of 31P-NMR, Kd was estimated to be 15 microM at pH 5.4, which is very close to that determined by ultrafiltration. While adenosine did not interfere with the binding. GTP, dCTP, ADP, UTP, AMP, phosphate and pyrophosphate were competitive inhibitors and their inhibition constants Ki were 25, 32, 36, 50, 130, 1000 and 186 microM, respectively. Fatty acids such as lauric acid and palmitic acid did not interfere with the binding. Warfarin was a non-competitive inhibitor. Cl- competitively inhibited the binding, and the inhibition constant was 20 mM. The dissociation constants of the Cl- binding were reported to be 0.42 mM for the first binding site, 10-5 mM for the second and 303-143 mM for the third [G. Scatchard, W.T. Yap, J. Am. Chem. Soc., 86 (1964) 3434; G. Scatchard et al., J. Am. Chem. Soc. 79 (1957) 12]. This suggests that the ATP binding site may be the second Cl- binding site.
Adenosine Triphosphate↗
Destabilization of peptide binding and interdomain communication by an E543K mutation in the bovine 70-kDa heat shock cognate protein, a molecular chaperone.
We have compared 70-kDa heat shock cognate protein (Hsc70) isolated from bovine brain with recombinant wild type protein and mutant E543K protein (previously studied as wild type in our laboratory). Wild type bovine and recombinant protein differ by posttranslational modification of lysine 561 but interact similarly with a short peptide (fluorescein-labeled FYQLALT) and with denatured staphylococcal nuclease-(Delta135-149). Mutation E543K results in 4. 5-fold faster release of peptide and lower stability of complexes with staphylococcal nuclease-(Delta135-149). ATP hydrolysis rates of the wild type proteins are enhanced 6-10-fold by the addition of peptide. The E543K mutant has a peptide-stimulated hydrolytic rate similar to that of wild type protein but a higher unstimulated rate, yielding a mere 2-fold enhancement. All three versions of Hsc70 possess similar ATP-dependent conformational shifts, and all show potassium ion dependence. These data support the following model: (i) in the presence of K+, Mg2+, and ATP, the peptide binding domain inhibits the ATPase; (ii) binding of peptide relieves this inhibition; and (iii) the E543K mutation significantly attenuates the inhibition by the peptide binding domain and destabilizes Hsc70-peptide complexes.
Adenosine Triphosphate↗
Laminin alpha2 chain-null mutant mice by targeted disruption of the Lama2 gene: a new model of merosin (laminin 2)-deficient congenital muscular dystrophy.
Using the gene targeting technique, we have generated a new mouse model of congenital muscular dystrophy (CMD), a null mutant for the laminin alpha2 chain. These homozygous mice, designated dy3Kldy3K, are characterized by growth retardation and severe muscular dystrophic symptoms and die by 5 weeks of age. Light microscopy revealed that muscle fiber degeneration in these mice begins no later than postnatal day 9. In degenerating muscles, considerable amounts of TUNEL positive nuclei were detected as well as DNA laddering, suggesting increased apoptotic cell death was involved in the process of muscle fiber degeneration.
Animals↗
Structural and functional domains of the troponin complex revealed by limited digestion.
Troponin (Tn), consisting of three subunits, TnT, TnC, and TnI, plays a crucial role in the calcium-dependent regulation of vertebrate striated muscle contraction. In the present study, we have applied limited proteolysis to the Tn complex in order to study domain structures and to detect conformational differences of Tn under different conditions. We found that both TnT and TnI were susceptible to chymotryptic digestion: while TnT was cleaved into TnT-(1-158)-peptide and TnT-(159-259)-peptide irrespective of Ca2+ concentration, the cleavage sites of TnI were dependent on the Ca2+ occupancy of TnC. In addition, we characterized the effects of depletion of the C-terminal part of TnI on acto-S1 ATPase activity. The TnT-(159-259)-peptide-TnC-TnICa-frag complex [TnICa-frag = (TnI-(1-134 and 1-140)-peptide], which was produced in the presence of CaCl2 and MgCl2, retains both the activating and inhibitory capabilities of whole Tn on the acto-S1 ATPase activity, while TnT-(159-259)-peptide-TnC-TnIMg-frag complex [TnIMg-frag = (TnI-(1-116)-peptide], which was obtained in the presence of MgCl2 and EGTA, lost its ability to activate acto-S1 ATPase activity. Our results indicate that residues 117-134 or 117-140 of TnI undergo structural changes upon Ca(2+)-binding to the regulatory sites of TnC and are necessary for the Ca(2+)-dependent inhibitory action of the Tn complex on acto-S1 ATPase activity. We also showed that residues 135-181 or 141-181 of TnI are involved in the interaction of Tn with the tropomyosin-actin filament.
Animals↗
Identification of a chick homologue of Fringe and C-Fringe 1: involvement in the neurogenesis and the somitogenesis.
In Drosophila, Serrate plays an important role to the wing margin formation. A putative secretory protein, Fringe, is indispensable for the wing margin formation inducing Serrate and other genes. Recently, Xenopus homologues of Fringe were identified and one of them, lunatic Fringe (X-lFng), was demonstrated to be involved in mesoderm induction. We have identified two chick Fringe homologous genes by reverse transcription-polymerase chain reaction and cDNA library screening. One of them, C-Fringe 1, showed sequence similarity to X-lFng. In situ hybridization study of C-Fringe 1 has demonstrated its expression in the developing nervous system and in the presomitic mesoderm. The hindbrain and spinal cord showed the distinct stripe pattern expression which was complementary to that of C-Serrate, indicating the correlation between them in vertebrate.
Amino Acid Sequence↗
Reduced X-ray resistance and homologous recombination frequencies in a RAD54-/- mutant of the chicken DT40 cell line.
rad54 mutants of the yeast Saccharomyces cerevisiae are extremely X-ray sensitive and have decreased mitotic recombination frequencies because of a defect in double-strand break repair. A RAD54 homolog was disrupted in the chicken B cell line DT40, which undergoes immunoglobulin gene conversion and exhibits unusually high ratios of targeted to random integration after DNA transfection. Homozygous RAD54-/- mutant clones were highly X-ray sensitive compared to wildtype cells. The rate of immunoglobulin gene conversion was 6- to 8-fold reduced, and the frequency of targeted integration was at least two orders of magnitude decreased in the mutant clones. Reexpression of the RAD54 cDNA restored radiation resistance and targeted integration activity. The reported phenotype provides the first genetic evidence of a link between double-strand break repair and homologous recombination in vertebrate cells.
Alkylating Agents↗
The transcriptional activity of a muscle-specific promoter depends critically on the structure of the TATA element and its binding protein.
We have previously characterized the proximal promoter of the mouse IIB myosin heavy chain (MyHC) gene, which is expressed only in fast-contracting glycolytic skeletal muscle fibers. We show here that the substitution into this promoter of a non-canonical TATA sequence from the IgH gene results in inactivity in muscle cells, even though TATA-binding protein (TBP) can bind strongly to this mutated promoter. Chemical foot-printing data show, however, that TBP makes different DNA contacts on this heterologous TATA sequence. The inactivity of such a non-canonical TATA motif in the IIB promoter context appears to be caused by a non-functional conformation of the bound TBP-DNA complex that is incapable of sustaining transcription. The conclusions imply that the precise sequence of the promoter TATA motif needs to be matched with the specific functional class of upstream activator proteins present in a given cell type in order for the gene to be transcriptionally active.
Amino Acid Sequence↗
An approximately half set of histone genes is enough for cell proliferation and a lack of several histone variants causes protein pattern changes in the DT40 chicken B cell line.
Of the 44 chicken histone genes, 39 are located in a major histone gene cluster of 110 kb, the others residing in four separate regions. The 42 sequenced genes encode six H1 variants, three H2A variants, four H2B variants, two H3 variants, and one histone H4. To clarify the influence on cell functions of simultaneous deletion of an approximately half set of the genes and some of the variants, we generated homozygous chicken DT40 mutants by disruption of two allelic segments of 57 kb, containing the 21 genes, using gene targeting techniques. Analyses with antisense RNA probes common or specific for gene families H1, H2A, H2B, H3 and H4 indicated that the remaining members of each of the gene families were expressed more in the mutants than in DT40 cells, resulting in maintenance of constant steady-state levels of mRNAs. Two-dimensional polyacrylamide gel electrophoresis showed that in the mutants several cellular proteins newly appeared or increased, and some other proteins disappeared or decreased quantitatively. These results demonstrate that all the histone gene families have the inherent ability to compensate for the disruption of a fair number of their own constituents. Furthermore, some of the histone variants are involved in regulation of the expression of putative genes that encode the proteins that varied in mutant DT40 cells, this participation is not compensated for by any residual variant of the same histone subtype(s).
Animals↗
Interactions between c-kit and stem cell factor are not required for B-cell development in vivo.
The receptor-type tyrosine kinase, c-kit is expressed in hematopoietic stem cells (HSC), myeloid, and lymphoid precursors. In c-kit ligand-deficient mice, absolute numbers of HSC are mildly reduced suggesting that c-kit is not essential for HSC development. However, c-kit- HSC cannot form spleen colonies or reconstitute hematopoietic functions in lethally irradiated recipient mice. Based on in in vitro experiments, a critical role of c-kit in B-cell development was suggested. Here we have investigated the B-cell development of c-kit-null mutant (W/W) mice in vivo. Furthermore, day 13 fetal liver cells from wild type or W/W mice were transferred into immunodeficient RAG-2-/- mice. Surprisingly, transferred c-kit- cells gave rise to all stages of immature B cells in the bone marrow and subsequently to mature conventional B2, as well as B1, type B cells in the recipients to the same extent as transferred wild type cells. Hence, in contrast to important roles of c-kit in the expansion of HSC and the generation of erythroid and myeloid lineages and T-cell precursors, c-kit- HSC can colonize the recipient bone marrow and differentiate into B cells in the absence of c-kit.
Animals↗
CD8 T cells from major histocompatibility complex class II-deficient mice respond vigorously to class II molecules in a primary mixed lymphocyte reaction.
Mature CD4+ and CD8+ T cells are restricted by major histocompatibility complex (MHC) class II and class I molecules, respectively. In a primary mixed lymphocyte reaction (MLR), CD8+ T cells from C57BL/6 (B6) mice can respond to allo-class I molecules, but not allo-class II molecules. However, a significant fraction of CD8+ T cells from C57BL/6 class II-deficient (B6Aalpha-) mice violate this rule by responding vigorously in a MLR to class II molecules. The frequency of responding cells is approximately 50% of that of B6 CD8+ T cells responding to B6bm1 allo-class I molecules. This response requires neither appropriate co-receptor, i.e. CD4, nor exogenous lymphokines, indicating that interactions between the T cell receptors (TCR) and class II molecules are remarkably efficient. Since these CD8+ T cells are positively selected by class I molecules in the thymus of class II-deficient mice, these CD8+ T cells should interact with both classes of MHC molecules. The absence of thymic negative selection by class II molecules may result in the production of these CD8+ T cells. The data imply that a substantial fraction of CD4+CD8+ double-positive thymocytes in wild-type mice interacts with both classes of MHC molecules prior to thymic selection.
Animals↗
Production, crystallization, and preliminary X-ray analysis of rabbit skeletal muscle troponin complex consisting of troponin C and fragment (1-47) of troponin I.
Troponin is a ternary protein complex consisting of subunits TnC. TnI, and TnT, and plays a key role in calcium regulation of the skeletal and cardiac muscle contraction. In the present study, a partial complex (CI47) was prepared from Escherichia coli-expressed rabbit skeletal muscle TnC and fragment 1-47 of TnI, which is obtained by chemical cleavage of an E. coli-expressed mutant of rabbit skeletal muscle TnI. Within the ternary troponin complex, CI47 is thought to form a core that is resistant to proteolytic digestion, and the interaction within CI47 likely maintains the integrity of the troponin complex. Complex CI47 was crystallized in the presence of sodium citrate. The addition of trehalose improved the diffraction pattern of the crystals substantially. The crystal lattice belongs to the space group P3(1)(2)21, with unit cell dimensions a = b = 48.2 A, c = 162 A. The asymmetric unit presumably contains one CI47 complex. Soaking with p-chloromercuribenzenesulfonate (PCMBS) resulted in loss of isomorphism, but enhanced the quality of the crystals. The crystals diffracted up to 2.3 A resolution, with completeness of 91% and R(merge) = 6.4%. The crystals of PCMBS-derivative should be suitable for X-ray studies using the multiple-wavelength anomalous diffraction technique. This is the first step for elucidating the structure of the full troponin complex.
Animals↗
Beta-adrenoceptor-linked signal transduction in ischemic-reperfused heart and scavenging of oxyradicals.
In order to examine the mechanisms of ischemia-reperfusion induced changes in beta-adrenoceptor-linked signal transduction pathway, isolated rat hearts perfused in the absence or presence of superoxide dismutase (SOD) plus catalase (CAT) were made ischemic for 30 min and then reperfused for 60 min. The left ventricular developed pressure as well as the rare of contraction and rate of relaxation were markedly decreased, whereas the left ventricular end-diastolic pressure increased in the ischemic hearts. A significant increase in the density and affinity of beta 1-adrenoceptors without any changes in the characteristics of beta 2-adrenoceptors was evident in cardiac membranes obtained from the ischemic hearts. The recovery of contractile abnormalities in the ischemic heart was depressed upon reperfusion; the ischemic-reperfused hearts also showed attenuated inotropic responses to isoproterenol. The affinities and densities of beta- and beta-adrenoceptors were decreased in the ischemic-reperfused hearts; the magnitude of changes in beta 1-adrenoceptors was greater than that in beta 2-adrenoceptors. The isoproterenol-stimulated adenylyl cyclase activity was depressed in both ischemic hearts and ischemic-reperfused hearts. The basal and forskolin-stimulated adenylyl cyclase activities were unaltered due to ischemia but were increased upon reperfusion. The NaF- and 5'-Guanylyl-imidodiphosphate[Gpp(NH)p]-stimulated adenylyl cyclase activities were depressed in the ischemic hearts and increased in the ischemic reperfused hearts. Cholera toxin (CT)-stimulated adenylyl cyclase as well as the CT-catalysed ADP-ribosylation activity and stimulatory G protein (Gs protein) immunoreactivity were decreased in the ischemic hearts and increased in the reperfused hearts. Pertussis toxin (PT)-stimulated adenylyl cyclase activity was unaltered in both ischemic and ischemic-reperfused hearts, whereas the PT-catalysed ribosylation and inhibitory G protein (Gi protein) immunoactivity were slightly increased in the reperfused myocardium. Thus the inability of isoproterenol to stimulate adenylyl cyclase in the ischemic-reperfused hearts may be due to alterations mainly in the characteristics of beta 1-adrenoceptors including density, affinity and coupling with the adenylyl cyclase. Scavenging of oxyradicals by the addition of SOD plus CAT in the perfusion medium prevented the reperfusion-induced changes in contractile function, inotropic responses of the heart to isoproterenol, activation of adenylyl cyclase by isoproterenol, as well as densities and affinities of beta-adrenoceptors in cardiac membranes. These results suggest that the depressed contractile activity and the attenuated inotropic responses of ischemic-reperfused hearts to isoproterenol as well as the defects in beta-adrenoceptor-linked signal transduction may be due to the formation of oxyradicals in the myocardium.
Adenylate Cyclase Toxin↗
Haemodynamic effects of hypotension induced by KRN2391 and nicardipine in isoflurane anaesthetized dogs.
PURPOSE: The investigational agent, KRN2391, is a potassium channel opener with a nitrate moiety which possesses potent vasodilatory action. We compared the haemodynamic effect of KRN2391. Induced hypotension with those of nicardipine. METHODS: Sixteen dogs were anaesthetized with isoflurane 1.3% in oxygen (1 MAC). After the baseline period. mean arterial pressure (MAP) was decreased to 60 mmHg for 60 min with an infusion nicardipine (n = 8). RESULTS: The KRN2391- and nicardipine-induced hypotension resulted in maximal decreased systemic vascular resistance of 35% and 25%, increases in cardiac index of 145% and 197%, and stroke volume index of 150% and 212%, respectively, (P < 0.01). There was no change in heart rate. Nicardipine was associated with increases (P < 0.01) in both right atrial and mean pulmonary artery pressures, whereas these variables remained unchanged with KRN2391. Pulmonary capillary wedge pressure decreased with KRN2391 (P < 0.01), but not with nicardipine. CONCLUSION: While both drugs were equally able of inducing hypotension, our results show that the haemodynamic profile of KRN2391- and nicardipine-induced hypotension was a hyperdynamic state expressed by the marked increase in cardiac index with varying changes in right and left ventricular filling pressures, and suggest that KRN2391 may be a useful vasodilator for induced hypotension.
Anesthesia, Inhalation↗
Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats.
S-1, a new oral antitumor agent, is composed of 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. FT which is a masked compound of 5-fluorouracil (5-FU) acts as an effector, while both CDHP and Oxo which do not have antitumor activity themselves act as modulators. In this study, the antitumor activity and intestinal toxicity of S-1 were investigated using experimental tumor models in rats, and compared with those of other oral fluoropyrimidines, namely 5-FU, FT, FCD (1 M FT/0.4 M CDHP) and UFT (combination of FT and uracil). In rats bearing subcutaneous Yoshida sarcoma, S-1 inhibited tumor growth at the lowest dose (ED50 value: S-1 5, UFT 22, FT 82, FCD 5, and 5-FU 19 mg/kg per day), and induced the least host body weight suppression, leading to the highest therapeutic index (TI) (S-1 4.5, UFT 1.4, FT 1.8, FCD 2.0, and 5-FU 1.4). S-1 also showed a higher therapeutic effect than UFT against AH-130 and Sato lung carcinoma. After administration of S-1 and UFT at equitoxic doses, S-1 showed a higher and more prolonged concentration of 5-FU than UFT both in plasma (AUC0-infinity: S-1 28 nmolh/ml, UFT 15 nmol.h/ml) and in tumor tissue (AUC0-infinity: S-1 95 nmolh/g tissue, UFT 52 nmolh/g tissue), leading to a higher 5-FU level incorporated into the RNA fraction (F-RNA level) in tumor tissue (AUC0-24: S-1 7.0 nmolh/mg RNA, UFT 4.3 nmolh/mg RNA) and 5-8% higher thymidylate synthase (TS) inhibition in tumor tissue at every time-point through 24 h. Compared with other oral fluoropyrimidines after administration of the maximal tolerable dose (MTD), S-1 caused the lowest rates of intestinal toxicities, such as diarrhea and occult blood in feces. S-1 also showed a higher antitumor effect on Yoshida sarcoma implanted intracolonically than UFT at an equitoxic dose (tumor weight: S-1 64 +/- 30 mg, UFT 133 +/- 52 mg; P < 0.05). These results suggest that CDHP, which is a potent inhibitor of 5-FU degradation, increases the antitumor activity of FT, and that Oxo, which is an inhibitor of 5-FU phosphorylation, locally protects the gastrointestinal tract from 5-FU-induced toxicity without decreasing the antitumor activity.
Animals↗
Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome-mediated endothelin-1 gene transfer.
BACKGROUND: Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 (ET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. METHODS: We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)-liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with beta-galactosidase gene was introduced. The expression of ET-1 and beta-galactosidase was assessed by immunohistochemistry. RESULTS: Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of beta-galactosidase gene, indicating beta-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. CONCLUSIONS: These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.
Animals↗
In situ expression and soluble form of P-selectin in human glomerulonephritis.
To clarify the early involvement of cellular adhesion molecules in human glomerulonephritis, we investigated P-selectin and high endothelial venules' (HEVs) marker MECA-79 expression in kidney specimens by immunohistochemical and in situ hybridization analyses, and measured serum and urinary soluble P-selectin levels by enzyme-linked immunosorbent assay. In normal controls, P-selectin and MECA-79 expression were negative in glomeruli (N = 4), and serum soluble P-selectin levels were 114.3 +/- 36.8 ng/ml (mean +/- SEM, N = 12). Soluble P-selectin was not detectable in urine of all cases. In proliferative glomerulonephritis involving rapidly progressive glomerulonephritis (N = 6), IgA nephropathy (N = 26), lupus nephritis (N = 7) and acute glomerulonephritis (N = 2), both glomerular and interstitial P-selectin expression were up-regulated. Glomerular P-selectin expression correlated positively with local cellular accumulation, endocapillary proliferation and CD41b (platelet) staining. Interstitial P-selectin expression showed a positive correlation with the grade of local cellular infiltrates. P-selectin mRNA signals detected by in situ hybridization were only observed on capillary or venous endothelium in the interstitium, but not in glomeruli. In addition, MECA-79 was expressed on the plump endothelial cells at the cortico-medullary junction (outer medulla). Serum soluble P-selectin levels were significantly higher in patients with proliferative glomerulonephritis, especially in glomerular and interstitial P-selectin positive staining, and correlated with glomerular endocapillary proliferation. These observations suggested that P-selectin was associated with both glomerular and interstitial leukocyte accumulation in human glomerulonephritis, and might be expressed by two distinct mechanisms that are the activated platelets in glomeruli and the de novo expression in the interstitial lesions that correlated with MECA-79 expression as HEVs like vessels, and serum soluble P-selectin may be a useful marker for predicting in situ P-selectin expression associated with glomerular endocapillary proliferation in nephritis.
Adult↗