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Biomedical subjects

Z Tian

Publications and source records attributed to Z Tian.

At least 19 recordsLinked to original sources
PubMed2006

The differential effects of low dose and high dose concanavalin A on cytokine profile and their importance in liver injury.

OBJECTIVE: Intravenous injection of concanavalin A (Con A) can cause mice to suffer from acute liver failure in a dose dependent manner and little is known about the difference between the high dose and the low dose of Con A regarding the immune response they initiate. The aim of this study was to analyze whether differential effects exist between the low dose and high dose of concanavalin A on the intrahepatic immune system and their importance in the development of liver injury. MATERIALS AND METHODS: A high dose of Con A (15 microg/g) was injected intravenously to induce murine hepatitis. A low dose of Con A (3 microg/g) was injected intravenously 12 h before the injection of the high dose of Con A (15 microg/g). Liver injury was evaluated by serum transaminase assay and H&E staining. Serum cytokine concentrations were determined by enzyme-linked immunosorbent assay (ELISA), intrahepatic cytokine and Fas mRNA levels by reverse transcriptase polymerase chain reaction. Intracellular cytokine expression and FasL expression were analyzed by flow cytometry and Fas protein expression in hepatocytes by Western-blotting. Intrahepatic apoptosis was evaluated by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). RESULTS: Low dose Con A injection induced a distinct cytokine expression profile, characterized by a preferentially elevated serum IL-6 at the early stage of stimulation, whereas high dose Con A injection provoked significant elevation of various cytokines involved in Con A-induced hepatitis. Pretreatment with a low, nonhepatoxic dose of Con A (3 microg/g) significantly decreased production of proinflammatory cytokines induced by the high dose Con A (15 microg/g). Furthermore, low dose Con A pretreatment could significantly decrease the serum levels of transaminases and liver necrosis induced by high dose of Con A. The intrahepatic Fas expression was also apparently reduced, accompanied by a decrease in hepatocyte apoptosis. CONCLUSION: Low dose Con A stimulation induced a different cytokine profile from high dose Con A stimulation resulting in differential importance in the development of liver injury.

Animals↗
PubMed2006

Central and/or peripheral immunoreactivity of orexin-A in pregnant rats and women.

Orexins (A and B) have been implicated in feeding behavior, energy balance and state of vigilance. During pregnancy, their involvement in feeding regulation and reproduction are poorly understood. In this study, we investigated orexin-A immunoreactivity in the hypothalamus and serum in pregnant rats and women by immunofluorescence staining, image analysis and radioimmunoassay, examined the correlation of serum orexin-A and leptin with gestational age in pregnant women by regression analysis, and explored the effect of leptin injected intracerebroventricularly (i.c.v.) on orexin-A immunoreactivity in the hypothalamus of normal rats by immunohistochemistry. The results showed that pregnant rats had significantly greater daily food intake on days 15 and 20 of pregnancy than virgin ones (+27.3%, P< 0.01 and +38.6%, P< 0.001 respectively), with significantly fewer number and lower mean staining intensity of orexin-A-immunoreactive (ir) neurons on days 16 (both P< 0.05) and 21 (both P< 0.01) of pregnancy. Moreover, serum levels of orexin-A exhibited 2.0-fold and 2.2-fold increases (both P< 0.001) in rats on days 16 and 21 of pregnancy compared with those in virgin rats, and 1.9-fold and 2.0-fold increases (both P< 0.001) in mid (13-26 weeks) and late pregnant women (27-40 weeks) compared with those in non-pregnant women. Simultaneously, serum levels of leptin showed a 2.3-fold and 2.2-fold increase (both P< 0.001) in rats on days 16 and 21 of pregnancy, and a 3.3-fold and 4.3-fold increase (both P< 0.001) in mid and late pregnant women. Serum levels of both orexin-A and leptin correlated positively with gestational age in pregnant women. Leptin injected i.c.v. significantly decreased the number (P< 0.01) and mean staining intensity (P< 0.01) of orexin-A-ir neurons in the hypothalamus, food intake (P< 0.01) and body weight gain (P< 0.001) compared with vehicle injection in normal rats. These results suggested that central and serum orexin-A might be involved in the regulation of feeding and energy metabolism during pregnancy. The change in central orexin-A immunoreactivity might be related to the increased serum leptin concentrations.

Animals↗
PubMed2005

Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus.

OBJECTIVES: Neurological abnormalities are present in some children after repair of congenital heart disease (CHD). Recently, structural brain abnormalities have been identified in infants prior to cardiac surgery. By altering in utero blood flow patterns, the type of CHD may impact upon cerebrovascular flow dynamics prior to birth. We sought to determine whether left- and right-sided obstructive congenital heart lesions modify cerebrovascular flow dynamics in the fetus. METHODS: Pulsed Doppler was used to measure blood flow velocities in the umbilical (UA) and middle cerebral (MCA) arteries in 172 fetuses from 20 to 39 weeks' gestational age referred for fetal echocardiography. Pulsatility index (PI), an indicator of downstream vascular resistance, was determined by (peak systolic velocity--end-diastolic velocity)/mean velocity. RESULTS: Fetuses with hypoplastic left heart syndrome (HLHS; n = 28) had decreased MCA-PI (P = 0.009) compared to normal fetuses (n = 114). Fetuses with right-sided obstructive lesions (RSOL; n = 17) had increased MCA-PI (P = 0.001) when compared to fetuses with HLHS. The UA-PI was elevated in fetuses with RSOLs (P = 0.045). CONCLUSIONS: Cerebrovascular resistance is lower than normal in fetuses with HLHS, a condition in which cerebral perfusion occurs retrograde via the ductus arteriosus. Fetuses with RSOL had significantly higher cerebrovascular resistance compared to fetuses with HLHS. The type of CHD impacts upon fetal cerebrovascular blood flow distribution and this may have implications for later development of neurological sequelae.

Blood Flow Velocity↗
PubMed2005

Activation and function of hepatic NK cells in hepatitis B infection: an underinvestigated innate immune response.

Natural killer (NK) cells are abundant in the normal liver, accounting for around one-third of intrahepatic lymphocytes and are important in the defence against hepatitis B virus (HBV) infection as innate immune responses. In this review, we discuss the mechanisms of hepatic NK cell activity against HBV. Whether directly activated by HBV infection or indirectly activated by other lymphocytes such as NKT cells or antigen-presenting cells (APCs), hepatic NK cells exert their anti-viral functions by natural cytotoxicity and production of high levels of cytokines. However, activated NK cells play an important role in regulating adaptive immune responses by interaction with other lymphocytes such as T, B and APCs. In addition, NK cells may contribute to the lymphocyte-mediated liver injury during HBV infection that was previously considered to be mediated only by CD8+ T cells or/and NKT cells.

Animals↗
PubMed2004

Central and peripheral immunoreactivity of melanin-concentrating hormone in hypothalamic obese and lactating rats.

Melanin-concentrating hormone (MCH) is believed to be an important orexigenic peptide mainly localized in the lateral hypothalamic area. Its involvement in the hyperphagia induced by hypothalamic lesions and lactation remains unclear. In this study, we investigated MCH immunoreactivity in the hypothalamus using immunohistochemistry and MCH concentration in the peripheral circulation using an enzyme immunoassay in rats with a lesion in the ventromedial hypothalamus or the paraventricular nucleus, and in lactating rats. Bilateral lesions of the ventromedial or paraventricular nuclei were performed using an electrolytic method. Quantification of immunoreactivity by image analysis revealed that the number and mean staining intensity of MCH-immunoreactive neurones in the lateral hypothalamic area and the zona incerta were significantly decreased by both types of lesions compared to sham controls, whereas circulating MCH concentration was not significantly different on day 7 postlesion. By contrast, in lactating rats on days 11-12 postpartum, the expression of MCH in the lateral hypothalamic area and the zona incerta was significantly increased compared to nonlactating controls. Circulating MCH concentration was not changed in lactating rats. These results suggest that hyperphagia induced by lactation, but not hypothalamic lesion, might be induced by excessive expression of MCH in the lateral hypothalamic area and the zona incerta.

Animals↗
PubMed2003

Preclinical studies of targeted alpha therapy for breast cancer using 213Bi-labelled-plasminogen activator inhibitor type 2.

The control of micrometastatic breast cancer remains problematic. To this end, we are developing a new adjuvant therapy based on (213)Bi-PAI2, in which an alpha-emitting nuclide ((213)Bi) is chelated to the plasminogen activator inhibitor-2 (PAI2). PAI2 targets the cell-surface receptor bound urokinase plasminogen activator (uPA), which is involved with the metastatic spread of cancer cells. We have successfully labelled and tested recombinant human PAI2 with the alpha radioisotope (213)Bi to produce (213)Bi-PAI2, which is highly cytotoxic towards breast cancer cell lines. In this study, the 2-day postinoculation model, using MDA-MB-231 breast cancer cells, was shown to be representative of micrometastatic disease. Our in vivo efficacy experiments show that a single local injection of (213)Bi-PAI2 can completely inhibit the growth of tumour at 2 days postcell inoculation, and a single systemic (i.p.) administration at 2 days causes tumour growth inhibition in a dose-dependent manner. The specific role of uPA as the target for (213)Bi-PAI2 therapy was determined by PAI2 pretreatment blocking studies. In vivo toxicity studies in nude mice indicate that up to 100 microCi of (213)Bi-PAI2 is well tolerated. Thus, (213)Bi-PAI2 is successful in targeting isolated breast cancer cells and preangiogenic cell clusters. These results indicate the promising potential of (213)Bi-PAI2 as a novel therapeutic agent for micrometastatic breast cancer.

Alpha Particles↗
PubMed2002

In vitro cytotoxicity of bismuth-213 (213Bi)-labeled-plasminogen activator inhibitor type 2 (alpha-PAI-2) on human breast cancer cells.

Metastasis is the principal cause of death in breast cancer patients. New and improved treatments for eradicating micrometastases are needed. To this end, a novel alpha-emitting protein construct, 213Bi-labelled plasminogen activator inhibitor type-2 (PAI-2) (alpha-PAI-2), was evaluated in vitro. This construct exploits: (a) the overexpression of the cell-surface receptor bound urokinase plasminogen activator (uPA) in the metastatic spread of breast cancer cells; (b) the binding and inhibition of receptor-bound uPA by PAI-2; and (c) the high cytotoxicity of alpha radiation. High labeling efficiencies and stability of 213Bi bound to human recombinant PAI-2 conjugated with cyclic diethylenetriaminepentaacetic acid anhydride were achieved (greater than 90%). The uPA inhibitory activity of the chelated PAI-2 was maintained as determined by complex formation with uPA and by inhibition of uPA activity. Furthermore, the reactivity of alpha-PAI-2 was confirmed in a cell assay as this construct was highly cytotoxic to breast cancer cell lines that express active, receptor bound uPA. The specificity of alpha-PAI-2 targeting was shown using several controls. Firstly, an active uPA blocking agent that limits PAI-2 binding significantly improved cell survival by a factor greater than three. Secondly, a non-specific alpha-BSA construct had minimal cytotoxic effect. Moreover, alpha-PAI-2 was not cytotoxic to freshly isolated normal human leukocytes, confirming that cells which do not contain active, receptor bound uPA cannot be targeted by alpha-PAI-2. In conclusion, we have validated, in vitro, the potential of alpha-PAI-2 as a novel therapeutic agent for breast cancer.

Bismuth↗
PubMed2002

In vitro and preclinical targeted alpha therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen.

Limited options for the treatment of prostate cancer have spurred the search for new therapies. One innovative approach is the use of targeted alpha therapy (TAT) to inhibit cancer growth, using an alpha particle emitting radioisotope such as (213)Bi. Because of its short range and high linear energy transfer (LET), alpha-particles may be particularly effective in the treatment of cancer, especially in inhibiting the development of metastatic tumors from micro-metastases. Prostate-specific membrane antigen (PSMA) is expressed in prostate cancer cells and the neovasculature of a wide variety of malignant neoplasms including lung, colon, breast and others, but not in normal vascular endothelium. The expression is further increased in higher-grade cancers, metastatic disease and hormone-refractory prostate cancer (PCA). J591 is one of several monoclonal antibodies (mabs) to the extracellular domain of PSMA. Chelation of J591 mab with (213)Bi forms the alpha-radioimmunoconjugate (AIC). The objective of this preclinical study was to design an injectable AIC to treat human prostate tumors growing subcutaneously in mice. The anti-proliferative effects of AIC against prostate cancer were tested in vitro using the MTS assay and in vivo with the nude mice model. Apoptosis was documented using terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridinetriphosphate [dUTP] nick end-labeling (TUNEL) assay, while proliferative index was assessed using the Ki-67 marker. We show that a very high density of PSMA is expressed in an androgen-dependent human PCA cell line (LNCaP-LN3) and in tumor xenografts from nude mice. We also demonstrate that the AIC extensively inhibits the growth of LN3 cells in vitro in a concentration-dependent fashion, causing the cells to undergo apoptosis. Our in vivo studies showed that a local AIC injection of 50 microCi at 2 days post-cell inoculation gave complete inhibition of tumor growth, whereas results for a non-specific AIC were similar to those for untreated mice. Further, after 1 and 3 weeks post-tumor appearance, a single (100 microCi/100 microl) intra-lesional injection of AIC can inhibit the growth of LN3 tumor xenografts (volume<100 mm(3)) in nude mice. Tumors treated with AIC decreased in volume from a mean 46+/-14 mm(3) in the first week or 71+/-15 mm(3) in the third week to non-palpable, while in control mice treated with a non-specific AIC using the same dose, tumor volume increased from 42 to 590 mm(3). There were no observed side effects of the treatment. Because of its in vitro cytotoxicity and these anti-proliferative properties in vivo, the (213)Bi-J591 conjugate has considerable potential as a new therapeutic agent for the treatment of prostate cancer.

Alpha Particles↗
PubMed2001

A high coking-resistance catalyst for methane aromatization.

Steaming-dealuminated HZSM-5-supported molybdenum catalysts have been found to be high coking-resistance catalysts for methane aromatization reactions; compared with conventional catalysts, they give a much higher selectivity towards aromatics.

Journal Article↗
PubMed2001

In vitro and preclinical studies of targeted alpha therapy (TAT) for colorectal cancer.

INTRODUCTION: Effective targeted cancer therapy requires high selectivity and cytotoxicity of the labelled product. We report the preparation and testing of anticolorectal cancer monoclonal antibody c30.6 radioimmunoconjugates (RIC) labelled with alpha-emitting Bismuth-213 and positron emitting Terbium-152 using two chelators, viz. Cyclic dianhydride of diethylenetriaminepentacetic acid (DTPA) and CHX-A" (a DTPA derivative). METHODS: Selectivity and stability of the RIC were tested in vitro (flow cytometry) and in vivo (biodistribution, organ/tumour uptake and retention). Cytotoxicity assays were carried out using tritiated thymidine uptake (inhibition of DNA synthesis) and MTS assay. RESULTS: High labelling efficiency (ranging between 89 and 91%) and stability over 2-5 half-lives of the isotopes were seen. Kidney retention was not seen in contrast to high uptake and retention of both conjugates in tumours. Flow cytometry studies showed high specificity of the antibody before and after labelling and this unchanged targeting behaviour was reflected in cytotoxicity assays. These assays showed that only alpha-labelled antibody could selectively kill the cancer cells for activities as low as 2-3 microCi. The study also revealed that free isotopes or isotopes bound to nonspecific antibodies did not kill cancer cells. CONCLUSION: The stability of the RICs and outstanding cytotoxicity of the alpha emitter, together with no kidney retention and high tumour uptake and retention of the radiolabel, offers a new approach for the potential control of colorectal cancer.

Journal Article↗
PubMed2001

Preclinical targeted alpha therapy for subcutaneous melanoma.

An alpha-emitting immunoconjugate (AIC) against malignant melanoma was prepared from the radioisotope bismuth-213 and a melanoma monoclonal antibody, and was used to control the growth of subcutaneous melanoma in a nude mouse model. Activity tolerances were found to be 8 mCi/kg for intraperitoneal injection of the conjugate, and 10 mCi/kg for intralesional injections. Local targeted alpha therapy (TAT) via intralesional injections of activities in the range 12.5-200 microCi shows a very high level of inhibition of tumorigenesis and regression of tumours. Results show that isolated cancer cells and preangiogenic cell clusters can be eliminated by local TAT, and that intralesional injections of 100 microCi of AIC are sufficient to cause complete regression of melanomas with volumes up to 300 mm3 without any observed side effects. Systemic TAT was less effective, with all tumours experiencing growth delay and limited inhibition of tumour growth. These data provide the basis for clinical trials of TAT in recurrent subcutaneous melanoma.

Animals↗
PubMed2001

The principle and technique of using Chinese drugs in the treatment of hypertension.

Differential use of Chinese and western drugs, and combination of traditional theory of materia medica with the results of modern pharmacological research can be regarded as a general principle in the treatment of a disease, while combination of lowering blood pressure with preventing and treating complications is a specific method in the treatment of hypertension. As to the use of drugs based on differentiation of diseases and/or symptoms, drugs which have the action of relieving symptoms but also reducing blood pressure should be used as the first choice. For those drugs which have the action of relieving symptoms but can not lower blood pressure should not be used or should be used as less as possible. Drugs with action of raising blood pressure are contraindicated. When patients have the symptoms of hyperactivity of yang resulting from yin deficiency, Huang Bo ([symbol: see text] Cortex Phellodendri) and Zhi Mu ([symbol: see text] Rhizoma Anemarrhenae) are used together to enhance the effects of both nourishing yin to reduce pathogenic fire, and reducing blood pressure. This practice conforms to the TCM theory and also to the modern pharmacological research.

Diagnosis, Differential↗
PubMed2001

[Effect of two extracted fraction from Lycopus lucidus on coagulation function].

OBJECTIVE: To find and define the effective fraction of Lycopus lucidus on coagulation. METHODS: Method of comparing turbidity, method of cutting a part of the mice tail and method of breaking glass tube. RESULTS: The two extracted fraction from lycopus lucidus F04-0A and F04-B could inhibit rats platlet aggregation in vitro and mice platelet aggregation in vivo. They could also prolong mice blood coagulation time. However, they had no effect on bleeding time. CONCLUSION: Both F04-A and F04-B had effects on inhibiting platelet aggregation and blood coagulation. Moreover, the activity of F04-A was probably stronger than that of F04-B. F04-A may be the effective fraction from Lycopus lucidus on promoting blood circulation and removing blood stasis.

Animals↗
PubMed2001

[The follow-up of 12 pregnant women with anticoagulation therapy after mechanical heart valve replacement].

OBJECTIVE: The article discusses the effect of warfarin on pregnant women and their fetus, and the methods of anticoagulation therapy during pregnancy. METHODS: The pregnancy, delivery, and anticoagulation therapy of 12 pregnant women with mechanical heart valve replacement were followed-up. RESULTS: All the patients received oral anticoagulant therapy during pregnancy. The mean dose of imported warfarin was (2.71 +/- 1.24) mg/d (4 cases); domestic warfarin, (3.14 +/- 0.28) mg/d (6 cases); domestic acenocumarol tablet (3.14 +/- 1.08) mg/d (2 cases). No thromboembolism and major hemorrhage occurred. A total of 8 person/times had minor bleeding. Ten patients had term delivery, 2 had premature birth, No abnormal fetus was observed. Only 1 newborn had low birth weight (2,100 g). CONCLUSION: The anticoagulation therapy with low dosage of warfarin (< 5 mg/d) is safe and convenient for the mothers during pregnancy following mechanical heart valve replacement and has low fetus abnormal rate.

Adult↗
PubMed2001

[Influence of HLA class I molecules expression on tumor cell resistance to NK lysis and the IFN-gamma regulatory effect].

OBJECTIVE: To investigate the relation between the NK lysis and HLA molecules expressed on the target cells as well as the regulatory effect of IFN-gamma. METHODS: The level of HLA-ABC molecules on seven human tumor cell lines were detected through the indirect immune fluorescence stain. NK lysis changes were observed after the blocking of HLA molecules on the target cells with the anti-HLA monoclonal antibodies or treating target cells with IFN-gamma. RESULTS: 1. Most of the tumor cell lines showed a complete or partial loss of HLA-ABC molecules, 2. After the HLA molecules had been marked on the target cells with the anti-HLA-ABC antibodies, the tumor cell susceptibility to the lysis of NK cells attack increased significantly and 3. After having being treated with IFN-gamma 500 U/ml for more than 48 hours, the HLA-ABC molecule levels on K562, M21 and PG cells went up. At the same time, their susceptibility to NK lysis was reduced. However, the resistance to Karpas, HL60 and HT29 NK lysis demonstrated a noticeable increase. The IFN-gamma promoted the apoptosis of HL60 and HT29 cells. CONCLUSION: The NK cells are capable of recognizing the HLA molecules on the target cells and show no lysis in providing a negative signal with the KIRs, an effect which the anti-HLA monoclonal antibodies are able to eliminate. IFN-gamma can be applied to make up for the loss of HLA molecules on some of the tumor cells, it can also facilitate some of the tumor cells' apoptosis.

Animals↗
PubMed2001

[Preparation and characteristics of human adherent natural killer cells induced by rhIL-15].

OBJECTIVE: This work was to do preliminary study on the characteristics and preparation of rhIL-15 induced adherent human natural killer cells (A-NK). METHODS: Natural killer cells (NK cells) were first separated by centrifugation on Ficoll-Hypaque gradients, plastic adherence and nylon wool column adherence. Then, they were further purified by Percoll discontinuous density gradient centrifugation and T cell panning. Fluorescence-activated cell scan (FACScan) was applied to evaluate the natural killer cells and assess their degree of purification. Then, the purified NKs were incubated in the presence of rhIL-2 (6,000 U/ml) or rhIL-15 (6,000 U/ml) and changed into adherent NK cells. In the next step, the adherent kinetics, proliferation and cytotoxicity of A-NKs obtained by two different cytokines were analyzed by cell counting, MTT and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The adherent percentage, cytotoxity and proliferation of A-NKs generated in rhIL-15 culture were higher than those in rhIL-2. CONCLUSION: IL-15 is a better stimulator than IL-2 to induce adherent natural killer cells.

Cell Adhesion↗
PubMed2001

[Randomized controlled trial for the effect of amrinone and aprotinin on proinflammatory cytokine release in patients with prosthetic valve replacement during perioperative period].

OBJECTIVE: To explore the effect of amrinone and aprotinin on whole-body inflammatory response in the patients with prosthetic valve replacement during perioperative period. METHODS: 24 patients undergoing prosthetic valve replacement were randomized to control group (group A, n = 8), aprotinin group (group B, n = 8) and amrinone combined with aprotinin group (group C, n = 8). In the aprotinin group, 3 x 10(6) of aprotinin was added to the priming solution of the extracorporeal circulation (ECC). In the amrinone combined with aprotinin group 3 x 10(6) of aprotinin was added to the priming solution of the ECC and amrinone began with a bolus of 1 mg/kg followed by a maintenance infusion of 8 micrograms/(kg.min). The control group received an equivalent prime volume without aprotinin. Venous blood samples were drawn before the operation, at the end of ECC, 1 hour after the end of ECC, and one day after the operation respectively. Enzyme-linked immunosorbent assay techniques were used to measure each of the cytokines. RESULTS: Before ECC, there were no differences of the levels of IL-6 and IL-8 among groups (P > 0.05). After ECC, the levels of IL-6 and IL-8 increased significantly in all groups (P < 0.05). The levels on day one after the operation were still higher than those before the operation in all groups (except the level of IL-8 in group C), but no statistical significance was observed. (P > 0.05). At 1 hour after the end of ECC, the level of IL-6 in group B was lower than that in group A, and the level of IL-6 in group C was lower than that in group B, but there was no statistically significant difference (P > 0.05); At the end of ECC, the level of IL-8 in group B was lower than that in group A and the level of IL-8 in group C was lower than that in group B, but no significant difference was noted (P > 0.05). It was also observed that the level of IL-8 was lower in group C than group A or B at 1 hour after the end of ECC. CONCLUSION: Although amrinone and aprotinin have antiinflammatory activity, but pump prime only aprotinin or aprotinin combined with amrinone may fall in preventing proinflammatory cytokine release (IL-6, IL-8) completely in patients with prosthetic valve replacement during ECC perioperative period.

Adult↗