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Biomedical subjects

S He

Publications and source records attributed to S He.

At least 127 records · Page 7Linked to original sources

Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility.

Protein C inhibitor (PCI) has been found in seminal plasma and is considered to protect intact surrounding cells and seminal plasma proteins from possible proteolytic damage. In the present study, we showed that although the antigenic levels of PCI in two seminal plasma samples from patients with infertility were normal or slightly elevated, their inhibitory activities toward urokinase plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) were absent. In contrast, uPA and tPA proteolytic activities in these two samples were 20-60-fold higher than that from normal volunteers. A time-course analysis of PCI-uPA complex formation showed that >80% of the complex had been formed within 15 min in normal seminal plasma in the presence of heparin, compared with the total complex formed after 150 min incubation, whereas no response to heparin stimulation was observed in the assays with the two patient samples. Similarly, >90% of PCI-tPA complex was formed after 30 min of heparin stimulation in normal seminal plasma but no response was observed in the two patient samples. Kinetic assays of PCI inhibitory function in the presence of activated protein C (APC) showed that PCI inhibitory activity in the two patient samples was absent and not stimulated by heparin. Western blotting also showed that most of the intact PCI molecules, in normal samples, formed complexes with either uPA or tPA but there was no complex formed in one of the two patient samples and very little complex was observed in the other, suggesting that PCI in the two patient samples is inactive. These results suggest that the presence of functionally inactive PCI in seminal plasma may be associated with infertility.

Adult↗

Can the laboratory assay of protein C activity assist in monitoring the hemostatic function in pre-eclampsia?

Published reports do not agree about whether protein C activity is non-significantly changed or decreased in a hypercoagulable state induced by pre-eclampsia without hemolysis-elevated liver enzyme/low platelet (HELLP) syndrome. In order to assess the relationship between this anticoagulant and enhanced hemostasis, levels of protein C activity, thrombin-antithrombin complexes, soluble fibrin, fibrin D-dimers and antithrombin were determined in 30 pre-eclampsia patients without the HELLP syndrome, in 22 normal pregnant women in gestational weeks 30-35, and in 13 non-pregnant controls. Levels of thrombin-antithrombin complexes, soluble fibrin and D-dimers increased (P < 0.05) whereas antithrombin decreased (P < 0.05) in patients with pre-eclampsia, compared with normal pregnant women. Levels of protein C did not differ significantly between patients with pre-eclampsia, normal pregnant women and controls (P > 0.05). The 5th and 95th percentiles of protein C levels in normal pregnant women were 0.53 and 1.30 U/ml, respectively; levels between these two values could be considered physiological. When the pre-eclampsia patients were subdivided according to these percentiles, none belonged to the subgroup with protein C < or = 5th percentile; 23% (seven of 30) fell into the subgroup with protein C > or = 95th percentile. Elevated levels of hypercoagulation markers were shown in the groups whose protein C fell within 5th-95th or > or = 95th percentiles (P < 0.05), compared with normal pregnant women. Concentrations of protein C and thrombin-antithrombin complex were significantly correlated (r = 0.69, P > 0.05) in patients with pre-eclampsia. In summary, in subjects with pre-eclampsia without the HELLP syndrome, protein C activity may be similar to that in normal pregnant women. However, such a 'physiological' anticoagulant level in association with the enhanced thrombin generation and fibrin formation does not necessarily reflect a physiological capability of coagulation. Thus, assays of protein C activity might not always assist in monitoring the hemostatic function during pre-eclamptic pregnancy.

Adult↗

Reassortment and insertion-deletion are strategies for the evolution of influenza B viruses in nature.

The evolution of influenza B viruses is poorly understood. Reassortment of influenza B viruses in nature as a means of genetic variation has not been considered to be a major contributor to their evolution. However, the current practice of assigning evolutionary relationships by antigenic analysis of the hemagglutinin of influenza B viruses would fail to detect reassortants. In this study, influenza B viruses isolated within the past 10 years from sites in the United States and China were studied by nucleotide sequencing of the hemagglutinin and neuraminidase genes and construction of phylogenetic trees to assess evolutionary relationships. A group of viruses represented by B/Houston/1/92 possess a hemagglutinin derived from a B/Yamagata/16/88-like strain and a neuraminidase derived from a B/Victoria/2/87-like strain. A second reassortment event between the hemagglutinin of a B/Yamagata/16/88-like virus closely related to the B/Beijing/184/93 strain and the neuraminidase of a B/Victoria/2/87-like strain is represented by a single virus, B/Memphis/3/93. The neuraminidase of the reassortant viruses is most closely related to that of B/Victoria/2/87-like viruses currently circulating in Nanchang, China. A pattern of insertions and deletions in the hemagglutinin and the neuraminidase of different strains of influenza B viruses is observed. Reassortment plays a role in the evolution of influenza B viruses and may necessitate a change in the methods used to assess and identify new influenza viruses.

Animals↗

Mutations affecting a yeast mitochondrial inner membrane protein, pnt1p, block export of a mitochondrially synthesized fusion protein from the matrix.

The machinery that inserts mitochondrially encoded proteins into the inner membrane and translocates their hydrophilic domains through the membrane is poorly understood. We have developed a genetic screen for Saccharomyces cerevisiae mutants defective in this export process. The screen is based on the fact that the hydrophilic polypeptide Arg8(m)p is exported from the matrix if it is synthesized within mitochondria as a bifunctional Cox2p-Arg8(m)p fusion protein. Since export of Arg8(m)p causes an Arg(-) phenotype, defective mutants can be selected as Arg(+). Here we show that mutations in the nuclear gene PNT1 block the translocation of mitochondrially encoded fusion proteins across the inner membrane. Pnt1p is a mitochondrial integral inner membrane protein that appears to have two hydrophilic domains in the matrix, flanking a central hydrophobic hairpin-like anchor. While an S. cerevisiae pnt1 deletion mutant was more sensitive to H(2)O(2) than the wild type was, it was respiration competent and able to export wild-type Cox2p. However, deletion of the PNT1 orthologue from Kluyveromyces lactis, KlPNT1, caused a clear nonrespiratory phenotype, absence of cytochrome oxidase activity, and a defect in the assembly of KlCox2p that appears to be due to a block of C-tail export. Since PNT1 was previously described as a gene affecting resistance to the antibiotic pentamidine, our data support a mitochondrial target for this drug.

Biological Transport↗

Haemostatic, endothelial and lipoprotein parameters and blood pressure levels in women with a history of preeclampsia.

To determine whether perturbations of haemostatic function and lipoprotein metabolism prevail long after preeclampsia and increase the risk of future coronary heart disease (CHD), we conducted a follow-up study in women with (cases, n = 25) or without (controls, n = 24) a history of preeclampsia. Blood samples were taken in the follicular and in the luteal phases of a menstrual cycle. Levels of blood pressure (BP) and proteinuria measured during the index pregnancy were included in the evaluation. Compared to control women who had undergone a normal pregnancy, the formerly preeclamptic patients had higher systolic (p <0.01) and diastolic (p <0.05) BPs and increased plasma levels of von Willebrand factor (vWF), fibrinogen, cholesterol, triglycerides and very low density lipoprotein (VLDL) (all p <0.05). The lipid, vWF, and fibrinogen levels were positively related to the degree of BP elevation but not to the degree of proteinuria during the index pregnancy. Except for the increase in vWF level, all biochemical perturbations were only present in the luteal but not in the follicular phase samples. In conclusion, persistent endothelial dysfunction with ensuing dysregulation of blood pressure, haemostatic perturbation and dyslipoproteinemia after preeclampsia may indicate a proneness to future CHD.

Adult↗

Mitral valve compensation for annular dilatation: in vitro study into the mechanisms of functional mitral regurgitation with an adjustable annulus model.

BACKGROUND AND AIM OF THE STUDY: Mitral annulus dilatation has been identified as an important factor in functional mitral regurgitation (FMR). However, the pathophysiologic interaction of annular dilatation and papillary muscle (PM) displacement in FMR, which occurs clinically in left ventricular (LV) dilatation, is still not well understood. It is difficult to separate these competing factors in vivo, leading to confusion in identifying the real role of the annular dilatation in FMR and its interaction with PM displacement. METHODS: To better understand the competing factors, an in vitro model was developed with a D-shaped adjustable mitral annulus that could be changed from 5.5 cm2 to 13.0 cm2 during experiments, independent of varying PM positions. Six excised normal porcine mitral valves were mounted in a left ventricular model with the adjustable annulus device and tested in a physiologic pulsatile flow system under normal cardiac output and left ventricular pressure (5.0 l/min, 120 mmHg). Papillary muscles were placed in normal and then displaced to an apical posterolateral position, to simulate pathological conditions seen clinically. Regurgitation was measured directly by a flow probe and the mitral valve geometry and leaflet coaptation were recorded by video camera through the model's atrium window. In addition, 2D echocardiography was used to evaluate leaflet coaptation and color Doppler flow mapping to detect the regurgitant flow field. RESULTS: The results showed that in normal PM position, the mitral regurgitant was consistently at low level until the annulus was enlarged to 1.75 times the normal size, at which time it increased sharply. Papillary muscle apical posterolateral displacement, which simulates a dilated LV, caused regurgitation to occur earlier (1.5 times the normal annulus size), and had an increased regurgitant volume (p < 0.05). The leaflet gaps were first observed at the commissural areas of the valves, consistent with the location of regurgitant jets detected by color Doppler flow mapping. Asymmetric PM displacement created more regurgitation than both the symmetric PM tethering (p = 0.063) and normal PM position (p < 0.01). The regurgitant jets were observed at the same commissural side as the PM displacement, even without significant enlargement of the annulus. CONCLUSIONS: This in vitro study provides insight into the interaction between annular dilatation and PM displacement on FMR. The resulting effects and their overall similarity to clinical observation could help further understand the mechanism of FMR and provide additional information to improve future therapeutic strategies.

Dilatation, Pathologic↗

A distinct integrin-mediated phagocytic pathway for extracellular matrix remodeling by RPE cells.

PURPOSE: To characterize the phagocytosis of extracellular matrix components by retinal pigment epithelial cells and to determine which receptors and signal transduction pathways are involved. METHODS: Fluorescent latex beads were coated with fibronectin (FN), collagen type I or IV, or thrombospondin and incubated with human retinal pigment epithelial cells for 3 hours. Phagocytosis was quantified by flow cytometry. The effects of adhesion blocking antibodies to cell surface receptors (alpha1, alpha3, alpha5, beta1, alpha5beta1, alphavbeta3, alphavbeta5 integrins and CD36) and inhibitors of specific intracellular signaling pathways (tyrosine kinase phosphatidylinositol 3-kinase [PI3-kinase], protein kinase C [PKC], and mitogen-activated protein kinase) were determined using FN-coated beads. RESULTS: Phagocytosis of FN-coated beads was greater than phagocytosis of beads coated with collagen type I, collagen type IV, or thrombospondin or uncoated controls (P < 0.0005). Anti-alpha5, -beta1, and -alpha5beta1 antibodies markedly inhibited FN phagocytosis (P < 0.0005); the inhibitory effects of anti-alpha5 antibody were stronger in the initial stages (binding) than in the later stages (internalization) of phagocytosis. There was no significant effect on phagocytosis when anti-alpha1, -alpha3, -alphavbeta5, -alphavbeta3 or -CD36 antibodies were used. Fibronectin phagocytosis was decreased by inhibitors of tyrosine kinase (genistein, 100 microg/ml, P < 0.005) and PI3-kinase (wortmannin, 5 microM, P < 0.01), but these reagents did not affect the uncoated controls. The PKC inhibitor calphostin C (400 nM) nonspecifically increased the phagocytosis of FN-coated (P < 0.05) and uncoated beads (P < 0.01). CONCLUSIONS: Subconfluent retinal pigment epithelial cells preferentially phagocytose FN over other extracellular matrix components. Phagocytosis of FN utilizes the alpha5beta1 integrin, is mediated in part through tyrosine kinase and PI3-kinase signaling pathways, and is modulated by PKC. Phagocytosis of extracellular matrix by retinal pigment epithelial cells may represent a novel mechanism for remodeling of the provisional extracellular matrix during outer retinal wound healing.

CD36 Antigens↗

Papillary muscle misalignment causes multiple mitral regurgitant jets: an ambiguous mechanism for functional mitral regurgitation.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to test the hypothesis that asymmetric alignment (misalignment) of the papillary muscles is sufficient to cause incomplete mitral leaflet coaptation and functional mitral regurgitation (MR). METHODS: Different spatial relationships between the papillary muscles and the mitral annulus were investigated in isolated porcine mitral valves in vitro to assess the impact on mitral valve competence. The systolic occlusional leaflet area (OLA) needed to cover the mitral orifice and the anterolateral (ACOM) and posteromedial (PCOM) commissural portion (OLA(ACOM), OLA(PCOM)) were assessed by 2D echocardiography to quantitate incomplete mitral leaflet coaptation. The regurgitant fraction (RF) and MR jet location were assessed by a flow meter and color Doppler ultrasound. RESULTS: Posterolateral dislocation of the posteromedial papillary muscle impaired mitral leaflet coaptation at the corresponding half-portion of the mitral orifice (OLA(PCOM): 351-397 mm2 versus 296 mm2 (normal); p < 0.001) and modified the contralateral part (OLA(ACOM): 354-387 mm2 versus 304 mm2 (normal); p <0.001). The mitral leaflet coaptation line moved in apical and posterior directions, creating a commissural MR orifice at the PCOM side. At the ACOM side, anterior leaflet prolapse and restricted posterior leaflet mobility created an additional commissural regurgitant jet (RF = 0.11-0.13). Symmetrical papillary muscle misalignment restricted mitral leaflet mobility on both sides of the orifice in a synergistic manner (OLA(PCOM): 416-459 mm2 and OLA(ACOM): 427-489 mm2; both p <0.001 versus normal). The central MR jet orifice, which extended towards both commissures, caused more significant MR (RF = 0.15-0.26). CONCLUSIONS: Papillary muscle misalignment caused mitral regurgitant jet ambiguity with an anterior MR jet location following posteromedial papillary muscle displacement. These findings may improve understanding of the relation between myocardial lesion and mitral regurgitant jet location and thereby facilitate rational strategies for valvular interventions.

Animals↗

Inhibitors of chymase as mast cell-stabilizing agents: contribution of chymase in the activation of human mast cells.

There has long been evidence that inhibitors of chymotryptic proteinases can inhibit the degranulation of rodent mast cells, but their actions on human mast cells and the contribution of mast cell chymase itself have received little attention. We investigated the ability of the selective chymase inhibitor Z-Ile-Glu-Pro-Phe-CO(2)Me and other proteinase inhibitors to inhibit chymase and cathepsin G activity, and we examined their potential to modulate the responsiveness of mast cells dispersed from human skin, lung, and tonsil tissues. IgE-dependent histamine release from skin mast cells was inhibited by up to about 80% after preincubation with Z-Ile-Glu-Pro-Phe- CO(2)Me (up to 0.1 microM), 70% with chymostatin (17 microM), and 60% with soybean trypsin inhibitor (0.5 microM). The mast cell-stabilizing properties of chymase inhibitors appeared to be greater for skin mast cells than for those from lung, whereas tonsil mast cells were relatively unresponsive. There were marked differences in the time course of responses to inhibitors, and the effect was dependent on the stimulus, with calcium ionophore-induced histamine release being unaffected. Incubation of dispersed skin, lung, or tonsil cells for up to 45 min with purified chymase failed to induce histamine release, although preincubation of cells with chymase was able to suppress IgE-dependent activation. Chymase could thus contribute to mast cell degranulation and after secretion could provide a feedback mechanism to limit this process. Nevertheless, inhibitors of chymase can be potent mast cell stabilizers, particularly in the skin.

Cathepsin G↗

Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs.

OBJECTIVE: To evaluate the toxic response to intrahepatic arterial administration of radioactive phosphorus-32 glass microspheres (32P-GMS) in domestic pigs. METHODS: Through selective catheterization of hepatic artery, 32P-GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31P-GMS was infused to other 5 healthy domestic pigs. Two pigs served as the whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 2, 4, 8 and 16, respectively, and liver biopsies were performed on the rest of pigs at the corresponding time points. Liver tissues from different sites were taken for light and electron microscopy. The ultrastructural histopathological changes were evaluated semiquantitatively. RESULTS: The accumulative amount of 32P-GMS in the target tissue attained more than 90% of the total dose administrated. Histologically, abnormal hepatocytes were easily found at week 1 or 2. At week 4 they were less than at week 1 or 2, and endothelium of the sinuses were damaged prominently. At week 8 they were scarcely seen, and liver tissue recovered gradually. The histological features of liver tissue restored to normal at week 16. Semiquantitative analysis of ultrastructural morphology in the experimental group showed no statistical difference (P > 0.50) between the nuclear abnormality (Nabn) and mitochrondrial variability (Mvar) at week 1 or 2, but revealed prominent difference (P < 0.01, P < 0.001) as compared with those in other groups. In the experimental group the Nabn in tissues showed no significant difference (P > 0.20) between week 8 and week 16. CONCLUSION: 32P-GMS internal irradiation at the dosage equivalent to human therapeutic dosage exerts reversible injury to domestic pig liver tissue, and it takes more than 8 weeks for the injured liver tissue to recover.

Animals↗

[Immunohistochemistry and DNA content of gastro-intestinal carcinoid].

OBJECTIVE: To study the relationship between clinical pathology and antigen expression and DNA content of gastrointestinal carcinoid tumors. METHODS: Fifty-two cases of paraffin-embedded gastrointestinal carcinoid specimens were collected. According to Gould's criteria, there were 20 cases of typical carcinoid, 20 cases of atypical carcinoid and 12 cases of undifferentiated carcinoid. Ten different kinds of antigen were examined by immunohistochemical staining and DNA contents by flow cytometry. RESULTS: Calcitonin (CT), carcinoembryonic antigen (CEA) and vasoactive intestinal peptide (VIP) expression was significantly reduced in typical carcionoid compared to that in other two types of carcionoid. Their expression was more marked in progression than in early stage of the disease. VIP expression was significantly higher in patients with than without lymph node metastases. Cellular DNA analysis showed significant difference between the typical and the other two types of carcinoid. Tumors with expression of VIP and CEA were mostly aneuploid. CONCLUSION: To study expression of relevant antigens in gastrointestinal carcinoid in relation to histological type and cellular DNA content helps determine its biologic behavior and prognosis.

Adult↗

[Cellular immune function influence on postoperative patients with hepatocellular carcinoma and the clinical effect of TILs treatment].

OBJECTIVE: To investigate the cellular immune function influence on postoperative patients with hepatocellular carcinoma (HCC) and clinical effect of TILs, rIL-2 and cyclophosphamide treatment. METHODS: Eight postoperative HCC patients were treated with TILs, rIL-2 and cyclophosphamide. Six patients were infused from the hepatic artery, and the other 2 infused from the portal vein. RESULTS: The IL-2 NK activity, Tsubsets, CD4(+)/CD8(+) level in the peripheral blood of all patients increased and the IL-6, TNF level of most patients decreased (P > 0.05, P < 0.01). For 6 - 18 month follow-up after management, 6 patients with radical tumor resection showed no recurrence. One patient having palliative resection showed no remnant tumor enlargement. One patient with increased TNF level for 8 IU died from hepatic failure 8 months after chemotherapy. CONCLUSIONS: The TILs, rIL-2 and cyclophosphamide treatment of postoperative HCC patients is effective in improving antitumorgenic immune function, preventing tumor recurrence, and restraining remnant tumor growth.

Adult↗

[Relationship between GSTM1 genotype and susceptibility to senile cataract].

OBJECTIVE: To study the relationship between the glutathione s-transferase gene deletion and cataract formation. METHODS: Blood cells of total of 77 cases with senile cataract and 76 controls were detected for GSTM1 gene, and the subcapsular epithelial cells of 22 cataract lenses were also detected for GSTM1 gene. RESULTS: The GSTM1 gene deletion rate in cataract group was 53.25% and that in the control group was 46.05%, they being not significantly different statistically (chi(2) = 0.750, P > 0.05, OR = 0.75). GSTM1 gene deletion rate in the subcapsular epithelial cells of 20 cases was basically consistent with that in blood cells. CONCLUSION: GSTM1 gene deletion is not related to senile cataract formation.

Aged↗

[Observation of the anterior ischemic optic neuropathy by color Doppler flow imaging].

OBJECTIVE: To study the characteristics of color Doppler flow imaging (CDFI) in anterior optic neuropathy (AION). METHODS: Forty eyes of 25 patients clinically diagnosed to have progressive AION were studied by using CDFI. The peak systolic velocity (PSV), end-diastolic velocity (EDV), time averaged maximum velocity (TAMV) and resistance index (RI) of the central retinal artery (CRA), nasal and temporal posterior ciliary arteries (PCAs) and ophthalmic artery (OA) were detected. The diameter of retrobulbar optic nerve (ON) was detected at the same time. Thirty-four volunteers were served as the control group. RESULTS: In the comparison with the control group, there were significantly reduced PSV, EDV and TAMV in PCAs (P < 0.001) and CRA (P < 0.001) and markedly increased RI in PCAs, CRA and OA in AION group. The retrobulbar optic nerve edema was found in 32/40 eyes. CONCLUSIONS: The characteristics of reduced velocity and increased resistance index in retrobulbar arteries of the AION are demonstrated. CDFI is helpful to the diagnosis of AION.

Adolescent↗

[Protect intercellular communication of pigment epithelium after laser photocoagulation].

OBJECTIVE: To observe the protective effect on the intercellular communication of retinal pigment epithelial (RPE) cells of dexamethasone (Dex) and verapamil (Ver) at different concentrations after laser photocoagulation. METHOD: Ten pig eyes were used to culture pig pigment epithelium cells. Use different concentrations of Dex and Ver to incubate cultured RPE cells 2 hours before laser coagulation, and then measure the intercellular communication function of confluent cells surrounding the coagulation spots after photocoagulation. RESULT: 125 mg/L Dex and 20 mg/L Ver could protect the intercellular communication of RPE cells under laser photocoagulation. The high concentration of drugs had better result. CONCLUSION: Both Dex and Ver can preserve the intercellular communication in vitro. The protective capacity is related to the concentration of drug.

Animals↗

[Studies on tannin and hydrolysate in three species of Chinese Caesalpinia plants].

OBJECTIVE: To get Chinese Caesalpinia plants that can replace the imported Tara to produce tannin and gallic acid. METHOD: Extract tannin with water, condense and hydrolyze the extracts with alkali, the hydrolysates were identified. Furthermore, an enlarged scale experiment was conducted. RESULT: Tannin contents of the plants were 32.2%, 46.6% and 58.5% respectively, the converted ratios of raw material to hydrolysate were 154:1, 11.8:1, 3.09-2.79:1 respectively. CONCLUSION: We got the Tara-replacing plants in Chinese Caesalpinia plants for the first time.

Caesalpinia↗