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Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 415 records · Page 23Linked to original sources
PubMed2000

CD4(+) T helper cells engineered to produce latent TGF-beta1 reverse allergen-induced airway hyperreactivity and inflammation.

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-beta abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-beta in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-beta was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-beta-secreting Th cells was antigen-specific and was reversed by neutralization of TGF-beta. Our results demonstrate that T cells secreting TGF-beta in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-beta-producing T cells play an important regulatory role in asthma.

Allergens↗
PubMed2000

Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone.

PURPOSE: Suramin is a novel agent that has demonstrated preliminary evidence of antitumor activity in hormone-refractory prostate cancer (HRPC). A prospective randomized clinical trial was designed to evaluate pain and opioid analgesic intake as surrogates for antitumor response in HRPC patients with significant, opioid analgesic-dependent pain. PATIENTS AND METHODS: A double-blind, placebo-controlled trial randomized patients to receive a 78-day, outpatient regimen of either suramin plus hydrocortisone (HC, 40 mg/d) or placebo plus HC. Treatment assignment was unblinded when either disease progression or dose-limiting toxicity occurred; placebo patients were allowed to cross-over to open-label suramin plus HC. In addition to pain and opioid analgesic intake, prostate-specific antigen (PSA) response, time to disease progression, quality of life, performance status, and survival were compared. RESULTS: Overall mean reductions in combined pain and opioid analgesic intake were greater for suramin plus HC (rank sum P =.0001). Pain response was achieved in a higher proportion of patients receiving suramin than placebo (43% v 28%; P =.001), and duration of response was longer for suramin responders (median, 240 v 69 days; P =.0027). Time to disease progression was longer (relative risk = 1.5; 95% confidence interval, 1.2 to 1.9) and the proportion of patients with a greater than 50% decline in PSA was higher (33% v 16%; P =.01) in patients who received suramin. Neither quality of life nor performance status was decreased by suramin treatment, and overall survival was similar. Most adverse events were of mild or moderate intensity and were easily managed medically. CONCLUSION: Outpatient treatment with suramin plus HC is well tolerated and provides moderate palliative benefit and delay in disease progression for patients with symptomatic HRPC.

Adult↗
PubMed2000

Cytological characterization of a pituitary folliculo-stellate-like cell line, Tpit/F1, with special reference to adenosine triphosphate-mediated neuronal nitric oxide synthase expression and nitric oxide secretion.

An immortal nonhormone-producing cell line with a characteristic star-shaped morphology, named Tpit/F1, was derived from an anterior pituitary gland of a temperature-sensitive large T antigen transgenic mouse. To characterize Tpit/F1 cells, we performed cytological studies, which revealed that Tpit/F1 cells express the messenger RNAs of neruonal nitric oxide (NO) synthase, S-100 protein, basic fibroblast growth factor, and pituitary-restricted transcription factor. The Tpit/F1 cells response to pituitary adenylate cyclase-activating peptide comprised the stimulated secretion of interleukin-6. Furthermore, glucocorticoids stimulate glutamine synthase production by Tpit/F1 cells. Considering these cytological characteristics together with their morphology, we deduced that Tpit/F1 cells are derived from pituitary folliculo-stellate (FS) cells. Our cytophysiological analyses of Tpit/F1 cells revealed that intracellular Ca2+ increased dose dependently on ATP administration (0-100 microM), and that this effect did not require the presence of extracellular Ca2+ and was not abolished by treatment with gadolinium, a Ca2+ channel blocker. The ATP-induced increase in intracellular Ca2+ ([Ca2+]i) was completely abolished by treatment with the Ca2+-adenosine triphosphatase (Ca2+-ATPase) inhibitor thapsigargin, which suggests that ATP increases [Ca2+]i by mobilizing internally stored Ca2+ followed by an influx of Ca2+. Moreover, UTP was equipotent with ATP in causing the [Ca2+]i increase in Tpit/F1 cells. Also, the Ca2+ response was prevented by the phospholipase C inhibitor, U-73122, but not by its inactive analog, U-73343. From these results we therefore concluded that ATP acts on Tpit/F1 cells via P2Y2-purinoceptors. Interestingly, both neuronal nitric oxide synthase messenger RNA and NO secretion were increased by ATP administration (10 and 100 microM). These results suggest the biological significance of the topological colocalization of FS cells and endocrine cells. Namely, ATP is cosecreted with hormones from endocrine cells and stimulates NO production by FS cells, and the released NO may regulate neighboring endocrine cell and blood vessels.

Adenosine Triphosphate↗
PubMed2000

Follistatin is a modulator of gonadal tumor progression and the activin-induced wasting syndrome in inhibin-deficient mice.

Inhibins and activins are dimeric proteins belonging to the transforming growth factor-beta superfamily. Follistatin is an activin-binding protein that antagonizes the function of activin via binding to its beta-subunits. Previously, we demonstrated that mice deficient in inhibin develop ovarian and testicular sex cord-stromal tumors of granulosa and Sertoli cell origin, with 100% penetrance as early as 4 weeks of age. Overproduction of activins in the serum directly causes a cachexia-like wasting syndrome that results in lethality of these mice at an early stage after the onset of the tumors. In an independent set of studies, overexpression of mouse follistatin using the mouse metallothionein I promoter in transgenic mice led to gonadal defects and eventual infertility, primarily due to local effects of follistatin in these tissues. Activin has a positive growth effect on gonadal tumor cells in culture and directly causes the cancer cachexia-like syndrome in inhibin-deficient mice via interaction with activin receptor type IIA in livers and stomachs. We therefore hypothesized that an activin antagonist such as follistatin can act as a physiological modifier, either locally or via the serum, to block the activin-mediated cancer cachexia-like syndrome in inhibin-deficient mice and/or slow the progression of gonadal cancers in these mice. To test this hypothesis, we generated mice that are homozygous mutant for the inhibin alpha null allele (i.e. inham1/inham1) and carry the mouse metallothionein I follistatin (MT-FS) transgene. Our results show that gonadal tumors that are histologically similar in most, but not all, cases to the tumors in inhibin-deficient mice develop in these inham1/inham1, MT-FS+ mice. However, inham1/inham1, MT-FS+ mice exhibit a less severe wasting syndrome, lower serum activin levels, and a statistically significant prolonged survival in a number of cases compared with mice deficient in inhibin alone. Thus, follistatin can act as a modulator of tumor growth and the activin-induced cancer cachexia-like syndrome in inhibin-deficient mice.

Activins↗
PubMed2000

Reactions of psoralen radical cations with biological substrates.

The reactions of several psoralen and coumarin radical cations with biological substrates such as nucleotides, amino acids and alkenes that serve as models for unsaturated fatty acids have been examined. The radical cations were generated by laser photoionization of the parent psoralen or coumarin in aqueous buffer in most cases. Easily oxidized substrates such as tyrosine, tryptophan and guanosine monophosphate react with the 8-methoxypsoralen and several methoxy-substituted coumarin radical cations with rate constants in excess of 2 x 10(9) M-1 s-1. In each case reaction occurs via electron transfer, as demonstrated by the observation of quencher-derived radical cations or radicals by transient absorption spectroscopy. For other substrates such as histidine, methionine and adenosine monophosphate the measured rate constants are significantly slower and vary with the oxidation potential of both the parent psoralen or coumarin and the quencher, again indicative of electron transfer reactivity. Most of the alkenes studied also react with the psoralen or coumarin radical cations via electron transfer, although there is some evidence for addition for linoleic acid. Product studies carried out using both lamp and laser irradiation in the presence of deoxyguanosine as a radical cation trap lead to the formation of characteristic base-derived Type-I (electron transfer) products. This lends support to our previous hypothesis that photoionization occurs via a monophotonic process and is thus relevant to conditions used in clinical phototherapeutic applications of psoralens. The results demonstrate the relevance of electron transfer chemistry to the use of psoralens and related compounds as photoactivated drugs.

Alkenes↗
PubMed2000

Pituitary adenylate cyclase-activating polypeptide acts synergistically with relaxin in modulating ovarian cell function in rats.

The interactive effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and relaxin on the secretion of gelatinases, involved in matrix remodeling, in ovarian theca-interstitial cells and granulosa cells, were investigated in gonadotropin-primed immature rats. The gelatinases secreted from cultured cells were analyzed using gelatin zymography and scanning densitometry. We have previously shown that relaxin stimulated the secretion of a 71 kDa gelatinase, identified as a type IV collagenase (matrix metalloproteinase 2), in rat theca-interstitial cells. This study has demonstrated that PACAP27 and PACAP38, with similar potency, dose-dependently enhanced relaxin-induced secretion of 71 kDa gelatinase, whereas PACAP alone had no effect. In rat granulosa cells, both PACAP27 and PACAP38 alone dose-dependently increased the secretion of a 63 kDa gelatinase. In addition, this study has shown that cAMP signaling pathway mediators act similarly to that of PACAP on gelatinase secretion in rat ovarian cells. Cholera toxin, forskolin and 8-bromoadenosine cAMP augmented relaxin-induced secretion of 71 kDa gelatinase in theca-interstitial cells, and alone they had no effect. These mediators also increased the secretion of 63 kDa gelatinase in granulosa cells. It is well known that the increase in cellular cAMP level is associated with the morphological rounding-up phenomenon in granulosa cells. This study has shown that PACAP and cAMP pathway mediators, but not relaxin, could cause such changes in cell shape in granulosa cells as well as in theca-interstitial cells. In conclusion, this study provides original findings that PACAP acts synergistically with relaxin in stimulating the secretion of gelatinases in rat ovarian theca-interstitial cells and granulosa cells. This supports the idea that relaxin and PACAP may serve as ovarian physiological mediators of gonadotropin function in facilitating the ovulatory process. In addition, PACAP appears to act through the cAMP signaling pathway to affect biological functions in ovarian cells, whereas relaxin does not.

Animals↗
PubMed2000

[The common C677T polymorphism in the methylenetetrahydrofolate reductase gene is associated with neural tube defects and preeclampsia].

OBJECTIVE: To assess whether methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphism is associated with neural tube defects and preeclampsia. METHODS: Twenty- four mothers who had given birth to normal children, 27 mothers who had given birth to NTDs children, 120 normal women, and 57 women who had suffered from preeclampsia were genotyped for C677T polymorphism by using PCR/RFLP method. RESULTS: (1) VV genotype frequency in the normal mothers group it was 0.13, while in the NTDs mothers group it was 0.33; mothers with VV genotype were at 3 times increased risk to have a NTDs child, compared with the normal mothers. (2) In the normal women group VV genotype frequency was 0.15, while in the preeclampsia women group it was 0.31; women with VV genotype were at 2.5 times increased risk to have preeclampsia, compared with the normal women. CONCLUSION: The authors believe that MTHFR VV genotype is associated with the development of NTDs and preeclampsia.

Female↗
PubMed2000

Transmural heterogeneity of myocardial contraction and ischemia. Diagnosis and clinical implications.

Myocardial contraction behaves heterogeneously, being greater in subendocardial than in subepicardial layers. Similarly, during acute myocardial ischemia or infarction, the subendocardium is the first myocardial layer to suffer. Conventional two-dimensional echocardiography cannot distinguish the transmural extension of myocardial ischemia or infarction, showing akinesia also when only the subendocardium is affected. Novel ultrasonographic techniques (like tissue characterization with integrated backscatter or Doppler tissue imaging) and nuclear magnetic resonance tagging can investigate myocardial contraction in different transmural layers and distinguish subendocardial from transmural ischemia or infarction. With the advent of thrombolysis and primary angioplasty in the acute phase of myocardial infarction a correct diagnosis of the extension of myocardial necrosis cannot ignore its transmural wavefront development. The salvage of the subepicardial layer does not give direct information on overall myocardial thickening but is one of the major determinants of overall left ventricular dysfunction and size. Although it is still necessary to investigate this phenomenon, new ultrasonographic techniques give us important information and more opportunities to appropriate diagnosis and future treatment of cardiac patients.

Animals↗
PubMed2000

[Effects of pravastatin on hepatic plasminogen activator inhibitor 1 mRNA expression in rabbits with fatty liver].

OBJECTIVE: To explore the effects of Pravastatin on the changes of plasminogen activator inhibitor 1 (PAI-1) gene expression of hepatic tissue in rabbit with fatty liver. METHODS: We observed the influences of Pravastatin on the rabbit model of hyperlipidemia and fatty liver induced by high fat diet for 12 weeks, and the plasma PAI-1 activity and the hepatic PAI-1 mRNA expression in therapeutic group (n=10); and meanwhile, designed the model group (n=10) and normal group (n=7) as control. RESULTS: Severe hepatocellular steatosis was found in model group compared with normal group. Plasma lipids and PAI-1 activity increased in model group in 6 and 12 weeks, and was significantly higher than normal group in 12 weeks. PAI-1 mRNA relative values in hepatic tissue in model group were higher than those in normal group. Compared with model group, hepatic pathological manifestation with the respect of steatosis had no obvious changes in therapeutic group, but the lipid content and PAI-1 activity in the plasma and the expression of PAI-1 mRNA in the liver were significantly reduced. The activity of PAI was (14.0A2. 5)X10(-3)U/L in model group, and (8.6A2.0)X10(-3)U/L in therapeutic group in 12 weeks. CONCLUSION: Pravastatin could inhibit over-expression of PAI-1 mRNA in the rabbit liver with hyperlipidemia and fatty liver, and reduce its plasma PAI-1 activity.

Animals↗
PubMed2000

Intranasal therapy with an adenoviral vector containing the murine interleukin-12 gene eradicates osteosarcoma lung metastases.

The purpose of these studies was to determine the effect of adenovirus-mediated interleukin-12 (IL-12) gene transfer on the growth and development of osteosarcoma (OS) lung metastases in nude mice. A nude mouse model was produced by repetitive cycling of human SAOS OS cells through the lung. The resultant SAOS-LM6 cell line produced microscopic lung metastases by 5-6 weeks after i.v. injection of the tumor cells, with visible lung metastases present 8 weeks after injection. Transfection of SAOS-LM6 cells with a plasmid containing the murine IL-12 gene resulted in a decrease in metastatic potential. Animals injected with IL-12-transfected clones had fewer metastases compared with mice injected with SAOS-LM6 cells transfected with a control plasmid. Furthermore, nasal delivery of an adenoviral vector containing the murine IL-12 gene resulted in the inhibition of pulmonary metastases. Together, these data indicate that IL-12 may be an effective agent against OS and that nasal delivery may offer a unique way to deliver the gene to the local tumor environment, potentially decreasing systemic toxic effects.

Adenoviridae↗
PubMed2000

Alcohol inhibits the progression as well as the initiation of atherosclerotic lesions in C57Bl/6 hyperlipidemic mice.

BACKGROUND: Evidence that a moderate consumption of alcohol is associated with a reduced incidence of and mortality due to coronary artery disease continues to accumulate. Despite recent evidence that substances in red wine confer resistance to coronary artery disease, it is clear that at least a substantial proportion of the protective effect is due to the alcohol content of the beverage. We have previously shown that the chronic ingestion of alcohol incorporated into a total liquid diet during a 24-week period inhibits the development of fatty streak lesions in hyperlipidemic C57Bl/6 mice. We have now repeated this study and demonstrated that alcohol continues to markedly inhibit atherogenesis during a 48-week period. METHODS: Mice were fed a high fat atherogenic liquid diet with 0% or 6% alcohol or a high fat atherogenic pelleted diet with 0% or 15% alcohol in their drinking water. After 24 and 48 weeks on these diets, subgroups of mice were euthanized and the aortas were studied for extent of atherosclerosis. Plasma lipid levels were also measured and flow cytometry studies performed to characterize their T and B lymphocyte populations. Additional groups of mice were given the high fat atherogenic diets for 24 weeks to allow lesions to develop and were then treated with alcohol diets to determine whether they inhibit the progression of the lesions. RESULTS: The alcohol diets suppressed the development of atherosclerotic lesions at both 24 and 48 weeks in both the liquid and pelleted diet models. The addition of the alcohol diets after allowing lesions to form for 24 weeks halted the further progression of the lesions. The alcohol treatments also decreased the plasma levels of total cholesterol and high density lipoprotein (HDL) cholesterol at almost all time intervals. CONCLUSIONS: We conclude that alcohol not only inhibits the initial development of atherosclerotic lesions but also inhibits the progression of existing atherosclerotic lesions. The alcohol-mediated decrease in HDL cholesterol in these experiments suggests that HDL plays little or no role in amelioration of atherogenesis in this model.

Animals↗
PubMed2000

[Study on hepatitis C virus infection of peripheral blood mononuclear cells in chronic hepatitis C patients].

OBJECTIVE: To demonstrate HCV infection and replication in the peripheral blood mononuclear cells (PBMCs) of hepatitis patients by the methods of molecular biology, immunology and electron microscopy. METHODS: HCV RNA and antigens were detected in the PBMCs of 28 patients with chronic hepatitis C by RT-PCR, Immunohistochemistry and electron microscopy, respectively. RESULTS: The positive rate of HCV RNA and HCV antigens were 77.27% (17/22) and 75.00% (21/28), respectively. Two types of spherical HCV-like particles with diameter of approximately 65 nm and 110 nm were observed in cytoplasmic vesicles by electron microscopy in the PBMCs with high titer of HCV RNA and antigens in 10 patients. The budding and shedding of these particles could also be found in the cytoplasmic vesicles. Immunoelectron microscopy using antibodies against HCV core and NS(3) demonstrated that the particles contained HCV antigens. CONCLUSION: HCV can infect and replicate in the PBMCs of patients with chronic hepatitis C.

Hepacivirus↗
PubMed2000

[One-pot synthesis of dl-naproxen by rearrangement].

AIM: To synthesize dl-naproxen by rearrangement method. METHODS: dl-Naproxen was synthesized by halogenation, ketalization, rearrangement and hydrolysis, using cupric halide as halogenation agent. RESULTS: Total yields were 74.0%-92.6% based on 6-methoxy-2-propionyl naphthalene. CONCLUSION: Total yield was higher by one-pot rearrangement approach.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Comparative study on efficacy of three sperm-separation techniques.

AIM: To evaluate the comparative effectiveness of real-time sperm separation technique (Wang's tube method) and other two conventional methods in isolating high-quality sperm preparation, and to compare the spouse pregnancy rate in intrauterine insemination (IUI) with sperm preparations isolated by these methods. METHODS: The effectiveness of the real-time sperm separation technique, the conventional swim-up and the Percoll discontinuous density gradient methods in isolating sperm preparations from 60 infertile patients (20 with apparently normal semen and 40, abnormal semen contaminated with microorganisms and other impurities) was evaluated and compared. The microorganisms to be removed included bacteria, virus, Chlamydia trachomaticum, Ureaplsama urealyticum, etc. The spouse pregnancy rates in IUI with sperm preparations isolated by these three techniques from 80 oligoasthenoteratospermic patients were also compared. RESULTS: The quality (including the percentages of normal form, normal-chromatin and motile sperm, and the grade of motility) of sperm obtained by the real-time sperm separation technique was much higher (P < 0.01) as compared with those by the other two methods. The Wang's tube method was also more effective in removing microorganisms and other impurities. The method provided a higher IUI pregnancy rate than the other two sperm separation techniques (P < 0.05). CONCLUSION: The real-time sperm separation technique is the most effective method so far available in isolating high-quality sperm samples to be used in assisted reproduction.

Adult↗
PubMed2000

[Protection of hematopoietic cells against toxicity of anticancer agents by transfecting mdr1 gene into bone marrow cells].

OBJECTIVE: To investigate whether the hematopoietic cells can be protected from the toxic effect of anticancer agents by transfecting mdr1 gene into bone marrow cells. METHODS: The mdr1 gene was transfected into murine and human bone marrow cells by Lipofectin. Expression of mdr1 was assessed by RT-PCR and flow cytometry. The functional activity of mdr1 in transfected cells was examined by rhodamine retention assay. Resistance to chemotherapeutic drugs of human and murine mdr1 gene transfected bone marrow cells was ascertained in vivo and that of murine cells was assessed in vivo in a bone marrow transplantation model. RESULTS: Multidrug resistance 1 gene was successfully transfected into and expressed in murine and human bone marrow cells. The transfected cells were resistant to doxorubicin; Vp-16, vincristine and colchicine. Bone marrow cells transfected with mdr1 gene reconstituted the hematopoietic function and offered resistance to doxorubicin in recipient mice. CONCLUSION: To transfect mdr1 gene into bone marrow cells is a promissing approach to protect bone marrow cells from the myelosuppressive effect of chemotherapeutic agents.

Animals↗
PubMed2000

Preliminary report on the effect of Nd: YAG laser irradiation on canine tooth pulps.

OBJECTIVE: To study the effects of Nd: YAG laser irradiation on the canine tooth pulps. METHODS: The crown pulp of dog was exposed and excised by ND: YAG laser irradiation. Histopathological examination was used to check changes of the tissues in root canal and periodontium. RESULTS: The pulp of the crown could be successfully excised by Nd: YAG laser without harmful changes in either root canal or periodontal tissues. CONCLUSION: This study may provide an experimental basis for the clinical possibility of crown pulp excision by using Nd: YAG laser irradiation.

Aluminum Silicates↗
PubMed2000

Effects of dihydroartemisinin on fine structure of erythrocytic stages of Plasmodium berghei ANKA strain.

AIM: The fine structural changes of Plasmodium berghei ANKA strain after treatment with the dihydroartemisinin (DATM) were observed. METHODS: DATM 180 mg.kg-1.d-1 was given ig to outbreed NIH mice infected with P. berghei ANKA strain. Blood samples were collected, embedded and examined by electron microscopy. RESULTS: In P. berghei ANKA strain, 1 h after drug administration, the parasites food vacuole membranes were destroyed, and the pigment grains showed some changes. The nucleus membrane, cytomembrane, and food vacuole membranes were stratified 2 h after administration. At the same time, swelling and separation of the outer and inner membrane or shrinking of the mitochondria were seen. Stripped nuclear and cytoplasm membrane were developed and vacuolizations were seen 4 h later. Eight hours after administration, a large number of parasite structures were destroyed except for a few parasite autophagic vacuoles. CONCLUSION: DATM was a fast-acting and effective antimalarial drug. Its primary target is the membrane system. No obvious resistant characteristics were found upto 24 generations after resistant induction test for 4 months.

Animals↗