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Biomedical subjects

J J Chen

Publications and source records attributed to J J Chen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Quinoline alkaloids and other constituents of Melicope semecarpifolia with antiplatelet aggregation activity.

Three new quinoline alkaloids, 2-acetylevolitrine (1), 2-acetylpteleine (2), and semecarpifoline (3), along with 26 known compounds were isolated from the root bark of Melicope semecarpifolia. The structures of 1-3 were elucidated by means of spectral analysis. In addition, (2S)-(--)-7,8-dimethoxyplatydesmine (4), cis-(+)-7,8-dimethoxymyrtopsine (5), and (3R)-(--)-8,9-dimethoxygeibalansine (6) were isolated as new natural products. Several of these isolates were determined as exhibiting significant antiplatelet aggregation activities in vitro.

Alkaloids↗
PubMed2001

Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity.

Fas ligand (CD95L) is synthesized both on the cell surface membrane and in a soluble form. Although CD95L contributes to immune privilege in the cornea and testis, the functions of these alternatively processed proteins are not well understood. Some reports suggest that the cytotoxicity of soluble CD95L is insignificant, whereas others show potent responses in vivo, including hepatocyte apoptosis that causes liver failure. We show here that extracellular matrix proteins interact with soluble CD95L and potentiate its pro-apoptotic activity. The cytotoxicity of supernatants from CD95L-expressing cells was increased by incubation on tissue culture plates coated with these matrix proteins; this effect was mediated by trimeric soluble CD95L. With the use of immunoprecipitation, it was found that CD95L binds directly to fibronectin. In addition, immunohistochemical analysis of the cornea revealed that soluble CD95L binds primarily to extracellular matrix. The retention of soluble CD95L on extracellular matrices is likely to play an important role in the development of peripheral tolerance in immune-privileged sites.

Animals↗
PubMed2001

Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells.

Digoxin (10(-7) - 10(-5) M) or digitoxin (10(-7) - 10(-5) M) decreased the basal and human chorionic gonadotropin (hCG)-stimulated release of progesterone from rat granulosa cells. Digoxin (10(-5) M) or digitoxin (10(-5) M) attenuated the stimulatory effects of forskolin and 8-bromo-cyclic 3' : 5'-adenosine monophosphate (8-Br-cAMP) on progesterone release from rat granulosa cells. Digoxin (10(-5) M) or digitoxin (10(-5) M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc)) activity (conversion of 25-hydroxyl cholesterol to pregnenolone) in rat granulosa cells but did not influence the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Neither progesterone production nor P450scc activity in rat granulosa cells was altered by the administration of ouabain. Digoxin (10(-5) M) or digitoxin (10(-5) M), but not ouabain, decreased the expression of P450scc and steroidogenic acute regulatory (StAR) protein in rat granulosa cells. The present results suggest that digoxin and digitoxin decrease the progesterone release by granulosa cells via a Na(+),K(+)-ATPase-independent mechanism involving the inhibition of post-cyclic AMP pathway, cytochrome P450scc and StAR protein functions.

Adenylyl Cyclases↗
PubMed2001

Monitoring metal ion contamination onset in hydrofluoric acid using silicon-diamond and dual silicon sensing electrode assembly.

Potentiometric detection of trace levels of metallic contamination onset in hydrofluoric acid using a silicon-based sensor in conjunction with two non-contaminating reference electrode systems is presented in this paper. In the first case, conductive diamond was used as a non-contaminating reference electrode. Cyclic voltammetry and open-circuit potential experiments demonstrated the feasibility of using a conductive diamond film electrode as a quasi-reference electrode in the HF solution. In the second case, a dual silicon electrode system was used with one of the silicon-based electrodes protected with an anion permeable membrane behaving as the quasi-reference electrode. The dual silicon sensing electrode system possessed an additional operational advantage of being unaffected by the solution acidity. Though both sensing configurations were able to detect the metal ion contamination onsets at the parts-per-trillion to parts-per-billion levels, the dual silicon electrode design showed a greater compatibility for the on-line detection of metallic impurities in HF etching baths commonly used in semiconductor processing.

Journal Article↗
PubMed2001

Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK.

Reperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons, which persists in vulnerable neurons, that is caused by the inhibition of translation initiation as a result of the phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha). To identify kinases responsible for eIF2alpha phosphorylation [eIF2alpha(P)] during brain reperfusion, we induced ischemia by bilateral carotid artery occlusion followed by post-ischemic assessment of brain eIF2alpha(P) in mice with homozygous functional knockouts in the genes encoding the heme-regulated eIF2alpha kinase (HRI), or the amino acid-regulated eIF2alpha kinase (GCN2). A 10-fold increase in eIF2alpha(P) was observed in reperfused wild-type mice and in the HRI-/- or GCN2-/- mice. However, in all reperfused groups, the RNA-dependent protein kinase (PKR)-like endoplasmic reticulum eIF2alpha kinase (PERK) exhibited an isoform mobility shift on SDS-PAGE, consistent with the activation of the kinase. These data indicate that neither HRI nor GCN2 are required for the large increase in post-ischemic brain eIF2alpha(P), and in conjunction with our previous report that eIF2alpha(P) is produced in the brain of reperfused PKR-/- mice, provides evidence that PERK is the kinase responsible for eIF2alpha phosphorylation in the early post-ischemic brain.

Animals↗
PubMed2001

A new tetrahydroprotoberberine N-oxide alkaloid and anti-platelet aggregation constituents of Corydalis tashiroi.

A new tetrahydroprotoberberine N-oxide alkaloid, (-)-cis-isocorypalmine N-oxide (1), together with two known compounds, 6-methoxydihydrosanguinarine (2) and norjuziphine (3), were isolated in continuing studies of the entire Formosan Corydalis tashiroi plant. The structures of these three compounds were determined through spectral analyses. In addition, compounds 1, 2, 3 and the seven alkaloids previously reported: (-)-cis-corydalmine N-oxide, (-)-trans-corydalmine N-oxide, (-)-trans-isocorypalmine N-oxide, scoulerine, protopine, oxysanguinarine and corydalmine, were found to possess antiplatelet aggregation activity.

Alkaloids↗
PubMed2001

Vasorelaxing and antioxidant constituents from Hernandia nymphaeifolia.

Three new alkaloids, (+)-nymphaedaline (1), oxo-O-methylbulbocapnine (2), and (+)-laetine (3), have been isolated from the trunk bark of Hernandia nymphaeifolia. The structures of these new compounds were elucidated by spectroscopic analysis. Among the isolates of this plant obtained till now, sixteen compounds show effective inhibitory activities on the contraction of vascular smooth muscles induced by high K+ (80 mM) or norepinephrine (3 microM). In addition, eight compounds showed effective antioxidant activities in scavenging the stable free radical, diphenyl-picryl-hydrazyl (DPPH).

Alkaloids↗
PubMed2001

A mechanistic approach to modelling the risk of liver tumours in mice exposed to fumonisin B1 in the diet.

Data from the National Toxicology Program's carcinogenesis study of fumonisin B1 in B6C3F1 mice, conducted at the National Center for Toxicological Research, were used to fit the Moolgavkar-Venzon-Knudson (MVK) two-stage, clonal-expansion model of carcinogenesis. In addition to tumour data from the conventional 2-year bioassay, the study included data on tissue weights, cell proliferation, cell death, and sphingolipid metabolism in primary target organs. The model was used to predict 2-year liver tumour rates in female and male mice based on differences among dose groups in the effect of fumonisin B1 on the growth of normal tissue and on the proliferation of preneoplastic cells as a compensatory response to sphinganine-induced cell death. Fumonisin B1 was assumed to be non-genotoxic, i.e. the model did not include any effect of fumonisin B1 on either of the two mutation rates of the MVK model. The model was able to reproduce reasonably well the observed tumour rates in both female and male mice, predicting substantially increased rates above background only at the highest doses of fumonisin B1 in females.

Animals↗
PubMed2001

Production of 25-hydroxycholesterol by testicular macrophages and its effects on Leydig cells.

Testicular macrophages secrete 25-hydroxycholesterol, which can be converted to testosterone by neighboring Leydig cells. The purposes of the present studies were to determine the mode of production of this oxysterol and its long-term effects on Leydig cells. Because oxysterols are produced both enzymatically and by auto-oxidation, we first determined if testicular macrophages possess cholesterol 25-hydroxylase mRNA and/or if macrophage-secreted products oxidize cholesterol extracellularly. Rat testicular macrophages had 25-hydroxylase mRNA and converted 14C-cholesterol to 14C-25-hydroxycholesterol; however, radiolabeled cholesterol was not converted to 25-hydroxycholesterol when incubated with medium previously exposed to testicular macrophages. Exposure of Leydig cells to 10 microg/ml of 25-hydroxycholesterol, a dose within the range known to result in high basal production of testosterone when tested from 1 to 6 h, completely abolished LH responsiveness after 2 days of treatment. Because 25-hydroxycholesterol is toxic to many cell types at 1-5 microg/ml, we also studied its influence on Leydig cells during 4 days in culture using a wide range of doses. Leydig cells were highly resistant to the cytotoxic effects of 25-hydroxycholesterol, with no cells dying at 10 microg/ml and only 50% of cells affected at 100 microg/ml after 2 days of treatment. Similar conditions resulted in 100% death of a control lymphocyte cell line. These results demonstrate that 1) testicular macrophages have mRNA for cholesterol 25-hydroxylase and can convert cholesterol into 25-hydroxycholesterol, 2) macrophage-conditioned medium is not capable of auto-oxidation of cholesterol, 3) Leydig cells are highly resistant to the cytotoxic influences of 25-hydroxycholesterol, and 4) long-term treatment with high doses of 25-hydroxycholesterol results in loss of LH responsiveness. These results support the concept that testicular macrophages enzymatically produce 25-hydroxycholesterol that not only is metabolized to testosterone by Leydig cells when present at putative physiological levels but also may exert inhibitory influences on Leydig cells when present for extended periods at very high concentrations that may occur under pathological conditions.

Animals↗
PubMed2001

Intraocular lens implantation after penetrating keratoplasty.

PURPOSE: We evaluated the clinical results of nonsimultaneous penetrating keratoplasty, cataract extraction, and intraocular lens (IOL) implantation (two-stage surgery) for combined corneal disease and cataract. METHODS: Twenty-six eyes of 24 patients with an average age of 46 years who underwent two-stage surgery were studied retrospectively. Variables included visual acuity, refractive status, specular microscopy before and after IOL implantation (6 months), and the occurrence of graft failure. Astigmatism was corrected by suture removal and relaxing incision. The mean follow-up after IOL placement was 16 months. RESULTS: Unaided visual acuity was 20/100 or better in 22 (83%) eyes after the second procedure. Twenty-one (81%) eyes had an aided visual acuity of at least 20/40. The mean refractive and absolute errors were -1.49 +/- 1.39 diopters (D) and 1.55 +/- 1.30 D, respectively. The mean keratometric and refractive cylinders were 3.50 D and 2.26 D, respectively. Nineteen (73%) eyes had a spherical equivalent refraction within 2 D of emmetropia. Anisometropia (> or =3 D) occurred in four (15%) eyes. The endothelial cell density, the coefficient of variation, and the percentage of hexagonal cells documented by specular microscopy were not significantly different before and after IOL implantation. Complications included three rejections, two cases of herpetic recurrence, and one late decompensation. Two graft failures (8%) occurred after secondary surgery. CONCLUSION: The two-stage surgery is a safe and effective modality.

Adolescent↗
PubMed2001

Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for eradication of Helicobacter pylori infection.

BACKGROUND: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively. In contrast, only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy. The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial. OBJECTIVES: To compare the results of two triple-therapy regimens, different only in the antisecretory drugs used, in patients with Helicobacter pylori infection, and to assess the impact of primary resistance to metronidazole on treatment outcome. METHODS: A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2-week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by a biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74-93%) in the OAT group. In the per protocol analysis, eradication therapy was achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%) treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79-96%) treated with OAT (not significant). The primary metronidazole resistance was present in 28.8% of strains. Overall, per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P > 0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or omeprazole, both combined with amoxycillin and tinidazole, are equally effective for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole resistance has no significant impact on eradication rates.

Adolescent↗
PubMed2001

Unconditional exact tests for equivalence or noninferiority for paired binary endpoints.

Problems of establishing equivalence or noninferiority between two medical diagnostic procedures involve comparisons of the response rates between correlated proportions. When the sample size is small, the asymptotic tests may not be reliable. This article proposes an unconditional exact test procedure to assess equivalence or noninferiority. Two statistics, a sample-based test statistic and a restricted maximum likelihood estimation (RMLE)-based test statistic, to define the rejection region of the exact test are considered. We show the p-value of the proposed unconditional exact tests can be attained at the boundary point of the null hypothesis. Assessment of equivalence is often based on a comparison of the confidence limits with the equivalence limits. We also derive the unconditional exact confidence intervals on the difference of the two proportion means for the two test statistics. A typical data set of comparing two diagnostic procedures is analyzed using the proposed unconditional exact and asymptotic methods. The p-value from the unconditional exact tests is generally larger than the p-value from the asymptotic tests. In other words, an exact confidence interval is generally wider than the confidence interval obtained from an asymptotic test.

Algorithms↗
PubMed2001

Tumor necrosis factor-alpha-induced cyclooxygenase-2 expression via sequential activation of ceramide-dependent mitogen-activated protein kinases, and IkappaB kinase 1/2 in human alveolar epithelial cells.

The role of p44/42 mitogen-activated protein kinase (MAPK), p38, and c-Jun NH(2)-terminal kinase (JNK) in tumor necrosis factor (TNF)-alpha-induced cyclooxygenase (COX)-2 expression was studied in NCI-H292 epithelial cells. TNF-alpha-mediated COX-2 expression and COX-2 promoter activity were inhibited by the MAPK kinase inhibitor PD98059 or the p38 inhibitor SB203580. Treatment of cells for 10 min with TNF-alpha resulted in activation of p44/42 MAPK, p38, and JNK. C2-ceramide (a cell-permeable ceramide analog), bacterial neutral sphingomyelinase (Smase; an enzyme that degrades sphingomyelin to ceramide), and N-oleoylethanolamine (a ceramidase inhibitor) all induced activation of MAPKs, COX-2 expression, nuclear factor (NF)-kappaB DNA-protein binding, and COX-2 promoter activity. The inactive analog, dihydro-C2-ceramide, had no effect. SMase- or C2-ceramide-induced COX-2 expression and COX-2 promoter activity were also inhibited by PD98059 or SB203580. Glutathione, a neutral SMase inhibitor, attenuated TNF-alpha- or SMase-induced activation of MAPKs, COX-2 expression, and COX-2 promoter activity. TNF-alpha- or C2-ceramide-induced COX-2 promoter activity was inhibited by the dominant negative mutant of extracellular signal-regulated kinase 2, p38, JNK, IkappaB kinase (IKK)1, or IKK2. IKK activity was stimulated by either TNF-alpha or C2-ceramide, and these effects were inhibited by PD98059 or SB203580. All these results suggest that, in NCI-H292 epithelial cells, activation of MAPKs by ceramide contributes to the TNF-alpha signaling that occurs downstream of neutral SMase activation and results in the stimulation of IKK1/2, and NF-kappaB in the COX-2 promoter, followed by initiation of COX-2 expression.

Cell Nucleus↗
PubMed2001

Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses.

Cytoplasmic stresses, including heat shock, osmotic stress, and oxidative stress, cause rapid inhibition of protein synthesis in cells through phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) by eIF2alpha kinases. We have investigated the role of heme-regulated inhibitor (HRI), a heme-regulated eIF2alpha kinase, in stress responses of erythroid cells. We have demonstrated that HRI in reticulocytes and fetal liver nucleated erythroid progenitors is activated by oxidative stress induced by arsenite, heat shock, and osmotic stress but not by endoplasmic reticulum stress or nutrient starvation. While autophosphorylation is essential for the activation of HRI, the phosphorylation status of HRI activated by different stresses is different. The contributions of HRI in various stress responses were assessed with the aid of HRI-null reticulocytes and fetal liver erythroid cells. HRI is the only eIF2alpha kinase activated by arsenite in erythroid cells, since HRI-null cells do not induce eIF2alpha phosphorylation upon arsenite treatment. HRI is also the major eIF2alpha kinase responsible for the increased eIF2alpha phosphorylation upon heat shock in erythroid cells. Activation of HRI by these stresses is independent of heme and requires the presence of intact cells. Both hsp90 and hsc70 are necessary for all stress-induced HRI activation. However, reactive oxygen species are involved only in HRI activation by arsenite. Our results provide evidence for a novel function of HRI in stress responses other than heme deficiency.

Animals↗
PubMed2001

How does HIV cause depletion of CD4 lymphocytes? A mechanism involving virus signaling through its cellular receptors.

HIV infection causes an acquired immunodeficiency, principally because of depletion of CD4 lymphocytes. The mechanism by which the virus depletes these cells, however, is not clearly understood. Since the virus predominantly infects CD4 lymphocytes in vivo, some have assumed that HIV replication directly kills the infected cells or that the anti-HIV immune response destroys them. However, a large number of studies do not support this concept. Rather, the data strongly indicate that CD4 lymphocyte depletion is by an indirect mechanism. Several theories on various direct and indirect mechanisms are reviewed. The most plausible mechanism, which is backed by in vivo data, involves the consequences of HIV contact with resting CD4 lymphocytes, which cannot support virus replication. HIV binding to, and signaling through, CD4 and chemokine receptor molecules on resting CD4 lymphocytes and other cell types [which extensively occurs as the rare, productively infected cells (ie: infected cells producing virus) migrate among other cells through the lymphoid tissues back into the blood] induces upregulation of L-selectin and Fas. When these resting, HIV-signaled CD4 cells return to the blood, they home very rapidly back to peripheral lymph nodes and axial bone marrow, and their disappearance from the blood is likely due to their leaving the circulatory system. Approximately one-half of these cells that have been induced by HIV to home to lymph nodes are subsequently induced into apoptosis during the process of trans-endothelial migration when secondary signals are received through various homing receptors. These cells are not making HIV, which would explain the observation that CD4 cells not making HIV are the predominant cells dying in the lymph nodes of HIV+ subjects. These studies indicate that the principal mechanism of CD4 T-cell depletion by HIV is due to its use of CD4 as its primary receptor and the signaling induced through this receptor on nonpermissive (resting) T-lymphocytes. This unique mechanism of viral pathogenesis, if correct, leads to the possibility that HIV might not cause depletion of CD4 lymphocytes if it used some other receptor to infect CD4 lymphocytes.

CD4-Positive T-Lymphocytes↗