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Biomedical subjects

X Hong

Publications and source records attributed to X Hong.

At least 37 records · Page 2Linked to original sources

Ceramides induce apoptosis in HeLa cells and enhance cytochrome c-induced apoptosis in Xenopus egg extracts.

Ceramide has been reported to induce typical apoptotic changes in nuclei incubated in a cell-free system, and that the addition of ceramide bypasses the requirement for mitochondria. Here, we explore the possible pathways by which ceramide induces apoptosis either in intact cells or in a cell-free system which we have developed. We found that in the cell-free system, C2-ceramide is not able to induce apoptosis in nuclei whereas cytochrome c does, but it is able to induce HeLa cells to undergo apoptosis. Ceramide is also not able to induce apoptosis when added into the cell-free system together with purified mitochondria. Further investigation showed that C2-ceramide at certain concentrations greatly increases nuclear apoptosis caused by cytochrome c in the cell-free system. From these results we conclude that the induction of apoptosis by ceramide may require intact cells in which some unknown signal transduction pathways are involved.

Animals↗

Intratumoral injection with [(188)Re]rhenium sulfide suspension for treatment of transplanted human liver carcinoma in nude mice.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Direct intratumoral injection of nonremovable radioactive material has been widely studied because it could deliver high doses of radiation to target sites and minimize radiation leakage to non-target organs or tissues. Thirty nude mice bearing SMMC 7721 human liver carcinoma were used for the biodistribution study after intratumoral injection of [(188)Re]rhenium sulfide suspension or sodium [(188)Re]perrhenate solution. Another 30 tumor-bearing mice were divided into six groups, four groups of which were treated with a 0.1 ml [(188)Re]rhenium sulfide suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral injection. For control studies, to study the tumor inhibiting ratio, the remaining two groups were injected with nonradioactive rhenium sulfide suspension and Hanks' balanced salt solution, respectively. The injections were repeated 6 days later. The retention percentages of radioactivity (%ID) in tumors injected with [(188)Re]rhenium sulfide suspension were 90.96+/-6.63%, 86.09+/-22.58% and 87.62+/-13.97% at 1, 24 and 48 h, respectively. Tumor inhibition ratios are as high as 89% when the outer space of tumor (0.5-0.6 cm from center) received about 507.6 Gy doses. Intratumoral injection of [(188)Re]rhenium sulfide suspension results in high tumor retention indicating this approach has strong potential for the treatment of hepatic carcinoma.

Animals↗

Nuclear apoptosis induced by isolated mitochondria.

We isolated and purified mitochondria from mouse livers and spinach leaves. When added into egg extracts of Xenopus laevis, they caused nuclei of mouse liver to undergo apoptotic changes. Chromatin condensation, margination and DNA ladder were observed. After incubating isolated mitochondria in some hypotonic solutions, and centrifuging these mixtures at high speed, we got mitochondrial supernatants. It was found that in the absence of cytosolic factor, the supernatant alone was able to induce apoptotic changes in nuclei. The effective components were partly of protein. DNA fragmentation was partly inhibited by caspase inhibitors AC-DEVD-CHO and AC-YVAD-CHO. Meanwhile, caspase inhibitors fully blocked chromatin condensation. Primary characterization of the nuclear endonuclease(s) induced by mitochondrial supernatants was also conducted. It was found that this endonuclease is different from endonuclease G, cytochrome c-induced nuclease, or Ca2+-activated endonuclease.

Animals↗

Chemical constituents of two Chinese Magnoliaceae plants, Tsoongiodendron odorum and Manglietiastrum sinicum, and their inhibition of platelet aggregation.

Phytochemical investigations of Tsoongiodendron odorum and Manglietiastrum sinicum, both Magnoliaceae, led to the isolation of twenty compounds in total. Among them, one was a new sesquiterpene, 11-O-oleoyl-beta-eudesmol (2), and another, 1-(3,4-dimethoxypheny)-4-(3,4-methylenedioxyphenyl)-2,3-dimethy lbutane (12) was isolated as a natural product for the first time. Moreover, 13C-NMR spectral data of isoguaiacin (16) are reported here for the first time. Structure elucidations for compounds reported here were mainly based on their spectral data. The ethanolic extracts of T. odorum and M. sinicum, and six pure compounds, 4(15)-eudesmen-11-ol (beta-eudesmol) (1), 1 beta-hydroxy-4(15),11(13)-eudesmadien-12,6 alpha-olide (reynosin) (3), 3,11(13)-eudesmadien-12,6 alpha-olide (alpha-cyclocostunolide) (5), erythro-1-(4-hydroxy-3-methoxyphenyl)-4-(3,4-methylenedioxyphenyl)-2,3- dimethylbutane (11), nectandrin-B (18), and syringaresinol (19), displayed considerable inhibition against platelet aggregation induced by AA, by ADP, or by PAF.

Humans↗

Structural revision of four spiramine diterpenoid alkaloids from the roots of Spiraea japonica.

On the basis of detailed 1H-NMR 13C-NMR spectral analysis, especially by 2D NMR experiments (1H-1H COSY, HMQC, HMBC, and NOESY) as well as by chemical transformations. four isoatisine type diterpenoid alkaloids, spiramines P and Q, and U and T, have been reassigned as the 6beta hydroxyl and 6beta acetoxyl substituents, respectively, rather than the previously assigned 15alpha counterparts in our further studies on chemical constituents of the roots of Spiraea japonica var. acuta.

Alkaloids↗

[The change of vWF in vascular endothelial cells under different stress].

AIM: To correlate the injury of vascular endothelial cells during various pathological conditions with the change of vWF (von Willebrand Factor) in different VEC lines. METHODS: Flow cytometer(FCM) were used to defect the immunoflourescent stained vWF in pulmonary artery endothelial cells (PAEC) of pig and aortic endothelial cells(AEC) of rats. RESULTS: The positive rates of vWF in PAEC of pigs is similar with that in AEC of rats under normal condition, but it decreased differently after hypoxic or cold injury. It was very interesting that the mean fluorescence intensity of positive PAEC or AEC exposed to hypoxia or cold elevated significantly compared with those of control. CONCLUSIONS: The change of vWF in VEC can be used to evaluate the function of VEC under different stress.

Animals↗

[Retroviral transduction of a mutant erbB-2 gene into human CD34+ derived dendritic cells].

OBJECTIVE: To successfully transduce a mutant erbB-2 gene into normal human CD34(+)-derived dendritic cells (DCs) and verify gene expression in these transduced dendritic cells. METHODS: The packaging cell line PA317 was transfected with mutant erbB-2 gene DNA and the virus produced was used to infect packaging cell line PG13. The virus produced by PG13 was used to infect CD34(+)-derived dendritic cells by the spinoculation method using flasks coated with fibronectin material to facilitate retrovirus gene transter efficiency and the mutant erbB-2 gene expression was assessed by ABC staining and FACScan methods. RESULTS: A mutant erbB-2 gene packaging cell line was produced and this mutant gene was transduced into human CD34(+)-derived DCs. It was verified that the relatively large numbers of the transduced DCs expressed the mutant erbB-2 protein which was eradicated of the ability to transform mouse NIH3T3 fibroblast cells. CONCLUSIONS: Human DCs can be gene-modified and these gene-modified DCs may be useful in stimulating T lymphocytes for immunotherapy.

3T3 Cells↗

[Epidemiological characteristics of Guillain-Barré syndrome in urban and rural areas in Beijing and Hebei, China].

OBJECTIVE: To investigate epidemiological and clinical patterns of Guillain-Barré syndrome (GBS) in urban and rural areas in Beijing municipality and Hebei province, China. METHODS: We investigated GBS incidence using a strengthened case surveillance and an active case ascertainment in 2 counties and 4 districts of Beijing municipality and 3 counties of Hebei province during 1993 to 1994. RESULTS: On the basis of the diagnostic criteria of NINCDS, 54 patients were identified. The age-adjusted incidence rates per 100,000 population for GBS were 0.9 in rural areas, and 0.8 in urban areas. A peak agespecific incidence showed in adults aged 50 to 59 years. A higher incidence appeared to occur in the spring and summer for rural residents, but not significant for urban population. In comparing course of GBS in rural and urban areas, there were differences in mean days from beginning of neurological symptom to maximal weakness (4.3 vs 7.6 days), and from symptom onset to beginning of recession (11.8 vs 17.5 days). There were preceding events in 72% patients, most frequently in respiratory infection, sensory disturbance in 70.9%, and respiratory assistance in 7.6%. The outcome was compatible with other reports; with complete recovery at 12 months in 79.2% and minimal residua in 20.8% for those alive and with casefatality rate in 7.4%. In addition, a follow-up study on electrophysiological features in 19(90.5%) patients from two counties of Beijing showed the demyelinating lesion (89.5%) over the axonal lesion (52.6%) of motor and/or sensory nerves. CONCLUSIONS: The epidemiological and clinical characteristics of GBS were similar to that reported in other countries. Demyelinating GBS was the main pattern in present population-based study.

Adolescent↗

Cytochrome c release and caspase activation during menadione-induced apoptosis in plants.

We report here the detection of the release of cytochrome c from mitochondria into the cytosol during menadione-induced apoptosis in tobacco protoplasts. Western blot analysis indicated that the caspase specific inhibitors AC-DEVD-CHO (Ac-Asp-Glu-Val-Asp-aldehyde) and AC-YVAD-CHO (N-acetyl-Try-Val-Ala-aspartinal) inhibited the degradation of a caspase 3 specific substrate PARP (poly(ADP-ribose) polymerase), and they had no effect on the release of cytochrome c. Further study showed that menadione could not induce apoptosis of mouse liver nuclei in tobacco cytosol extract containing no mitochondria. However, when cytochrome c or mitochondria was added into the cytosol extract, apoptosis of mouse liver nuclei and the degradation of PARP could both be detected. The results provide strong evidence that menadione can induce apoptosis in tobacco protoplasts via the release of cytochrome c from mitochondria into the cytosol.

Animals↗

Design and synthesis of novel dihydropyridine alpha-1a antagonists.

A series of analogs of SNAP 5150 containing heteroatoms at C2 or C6 positions is described. Herein, we report that the presence of alkyl substituted heteroatoms at the C2(6)-positions of the dihydropyridine are well tolerated. In addition, 15 inhibited the phenylephrine induced contraction of dog prostate tissue with a Kb of 1.5 nM and showed a Kb (DBP, dogs, microg/kg)/Kb (IUP, dogs, microg/kg) ratio of 14.8/2.5.

Adrenergic Antagonists↗

Clinical applications of the Shack-Hartmann aberrometer.

The efficacy of the Shack-Hartmann technique for measuring the optical aberrations of the eye was evaluated for four classes of clinical conditions associated with optically abnormal eyes. These categories (with specific examples) are: anomalies of the tear film (dry eye), corneal disease (keratoconus), corneal refractive surgery [laser-assisted in situ keratomileusis (LASIK)], and lenticular cataract. We show that in each of these cases, it is possible to obtain at least a partial topographic map of the refractive aberrations of the patient's eyes, but severe losses of data integrity can occur. We further show that the Shack-Hartmann aberrometer provides additional information about the eye's imperfections on a very fine spatial scale (< 0.4 mm) which scatter light and further degrade the quality of the retinal image. Taken together, spatial maps of the variation of optical aberrations and scatter across the eye's entrance pupil represents an improved description of the optical imperfections of the abnormal eye.

Cataract↗

Identification and characterization of the human orthologue of yeast Pex14p.

Pex14p is a central component of the peroxisomal protein import machinery, which has been suggested to provide the point of convergence for PTS1- and PTS2-dependent protein import in yeast cells. Here we describe the identification of a human peroxisome-associated protein (HsPex14p) which shows significant similarity to the yeast Pex14p. HsPex14p is a carbonate-resistant peroxisomal membrane protein with its C terminus exposed to the cytosol. The N terminus of the protein is not accessible to exogenously added antibodies or protease and thus might protrude into the peroxisomal lumen. HsPex14p overexpression leads to the decoration of tubular structures and mislocalization of peroxisomal catalase to the cytosol. HsPex14p binds the cytosolic receptor for the peroxisomal targeting signal 1 (PTS1), a result consistent with a function as a membrane receptor in peroxisomal protein import. Homo-oligomerization of HsPex14p or interaction of the protein with the PTS2-receptor or HsPex13p was not observed. This distinguishes the human Pex14p from its counterpart in yeast cells and thus supports recent data suggesting that not all aspects of peroxisomal protein import are conserved between yeasts and humans. The role of HsPex14p in mammalian peroxisome biogenesis makes HsPEX14 a candidate PBD gene for being responsible for an unrecognized complementation group of human peroxisome biogenesis disorders.

Amino Acid Sequence↗

Fast scan and echo planar MR imaging technology.

The development of imaging technology for acquiring ever-faster images has been an ongoing activity since the early years of MR imaging development. This article gives the reader a sense of the range of technical challenges faced by the developers of faster imaging hardware and some of their solutions. Before reviewing the technical issues, however, the authors briefly discuss the marketplace realities that have led to technology decisions and, to a certain extent, the prolonged pace of development of the hardware.

Amplifiers, Electronic↗

Autologous high-killing cytotoxic T lymphocytes against human lung cancer are induced using interleukin (IL)-1beta, IL-2, IL-4, and IL-6: possible involvement of dendritic cells.

Although CTLs bear main immune responses in human tumors, stable CTL clones against human lung cancer have rarely been generated. Our previous study demonstrated efficient autologous CTL induction in human gastric cancer and glioblastoma by cytokine combination of interleukin (IL)-1beta (167 IU/ml), IL-2 (67 IU/ml), IL-4 (67 IU/ml), and IL-6 (134 IU/ml). In this study, we demonstrated successful induction of autologous stable CTLs in five of six patients with lung adenocarcinoma from mixed-lymphocyte tumor culture using this cytokine combination. All CTLs revealed potent and specific killing activity against autologous target cells (over 75% in CD8+ CTLs and over 50% in CD4+ CTLs at an E:T ratio of 10 for 24 h). Using a series of antibodies, CD8+ CTLs showed to recognize tumor-specific antigens of lung cancer cells through HLA class I. In the separate experiments, failure of CTL induction from monocyte-depleted peripheral blood mononuclear cells and appearance of cells with characteristics of dendritic cells from adherent peripheral blood mononuclear cells in the culture of the same concentration of IL-1beta, IL-4, and IL-6 indicated that CTLs can be efficiently generated by this cytokine combination via possible dendritic cell induction. This is the first study of an efficient and reproducible in vitro CTL induction against human lung cancer.

Adenocarcinoma↗

Design and synthesis of novel alpha1a adrenoceptor-selective dihydropyridine antagonists for the treatment of benign prostatic hyperplasia.

We report the synthesis and evaluation of novel alpha1a adrenoceptor subtype-selective antagonists. Systematic modification of the lipophilic 4,4-diphenylpiperidinyl moiety of the dihydropyridine derivatives 1 and 2 provided several highly selective and potent alpha1a antagonists. From this series, we identified the 4-(methoxycarbonyl)-4-phenylpiperidine analogue SNAP 5540 (-) [(-)-63] for further characterization. When examined in an isolated human prostate tissue assay, this compound was found to have a Ki of 2.8 nM, in agreement with the cloned human receptor binding data (Ki = 2.42 nM). Further evaluation of the compound in isolated dog prostate tissue showed a Ki of 3.6 nM and confirmed it to be a potent antagonist (Kb = 1.6 nM). In vivo, this compound effectively blocked the phenylephrine-stimulated increase in intraurethral pressure (IUP) in mongrel dogs, at doses which did not significantly affect the arterial pressure (diastolic blood pressure, DBP), with a DBP Kb/IUP Kb ratio of 16. In addition, (-)-63 also showed greater than 40 000-fold selectivity over the rat L-type calcium channel and 200-fold selectivity over several G protein-coupled receptors, including histamine and serotonin subtypes. These findings prove that alpha1a adrenoceptor-subtype selective antagonists such as (-)-63 may be developed as uroselective agents for an improved treatment of BPH over nonselective alpha1 antagonists such as prazosin and terazosin, with fewer side effects.

Adrenergic alpha-1 Receptor Antagonists↗

Analysis of primate renal allografts after T-cell depletion with anti-CD3-CRM9.

BACKGROUND: FN18-CRM9 is a CD3-specific immunotoxin that is capable of depleting CD3+ T cells. Pretreatment of rhesus monkeys with this agent before transplantation can induce donor-specific tolerance and "split tolerance" to renal allografts. METHODS: Heterotopic renal transplants were performed on monkeys that received posttransplant FN18-CRM9. Histological and immunohistological staining, as well as analysis of the intragraft cytokine profile by reverse transcriptase polymerase chain reaction, was performed on percutaneous allograft biopsies. RESULTS: Experimental monkeys had significant prolongation of allograft survival. Although an interstitial, mononuclear cell infiltrate was seen in all of the renal transplants, there was minimal evidence of acute cellular rejection. Histological evidence of alloantibody-mediated damage was detected 3 to 5 months after transplantation in the monkeys treated with FN18-CRM9. Immunohistology demonstrated the reappearance of CD3+ and CD4+ T cells, as well as CD20+ B cells, in the grafts. Cytokine analysis demonstrated expression of interferon-gamma. An intact anti-donor IgG response was seen. CONCLUSION: Treatment of monkeys with FN18-CRM9 immediately after transplantation significantly prolongs renal allograft survival. Allograft biopsies demonstrate a lack of acute cellular rejection; however, alloantibody-mediated graft damage and rejection occur, with an intact anti-donor IgG response. The intragraft expression of the interferon-gamma may reflect this ongoing humoral rejection. These data suggest that even a brief period of T-cell allosensitization may lead to humorally mediated allograft damage. Efforts to achieve tolerance with posttransplant FN18-CRM9 will require modification of the protocol to deplete T cells before allosensitization exposure or to supplement the posttransplant immunomodification strategy.

Animals↗

Identification of a dihydropyridine as a potent alpha1a adrenoceptor-selective antagonist that inhibits phenylephrine-induced contraction of the human prostate.

A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate.

Adrenergic alpha-Agonists↗