Biomedical subjects

H Zhu

Publications and source records attributed to H Zhu.

At least 325 records · Page 18Linked to original sources

PubMed1998

Alternative promoters and cardiac muscle cell-specific expression of the Na+/Ca2+ exchanger gene.

Many studies have investigated the regulation of the Na+/ Ca2+ exchanger, NCX1, but limited data exist on transcriptional regulation of the NCX1 gene. We have identified the transcription start sites of three tissue-specific alternative promoters of NCX1 transcripts from rat heart, kidney, and brain. We have characterized the cardiac NCX1 promoter, from which the most abundant quantities of NCX1 transcripts are expressed. Transfection of primary cardiac myocytes, CHO cells, and COS-7 cells with overlapping genomic DNA fragments spanning the NCX1 cardiac transcription start site has uncovered a cardiac cell-specific minimum promoter from -137 to +85. The cardiac NCX1 promoter is TATA-less but has putative binding sites for cardiac-specific GATA factors, an E box, and an Inr as well as multiple active enhancers. The kidney NCX1 promoter has a typical TATA box and binding sites for several tissue-specific factors. The brain NCX1 promoter is very GC-rich and possesses several Sp-1 binding sites consistent with its ubiquitous expression.

Alternative Splicing↗

PubMed1998

Erythropoietin: a model system for studying oxygen-dependent gene regulation.

The physiological regulation of the red cell mass depends upon enhanced transcription of the erythropoietin (Epo) gene in response to hypoxia. Studies of Epo gene expression have been useful in investigating the mechanism by which cells and tissues sense hypoxia and respond with biologically appropriate alterations in gene expression. It is likely that oxygen sensing involves a heme protein in which cobalt and nickel can substitute for iron in the porphyrin ring. Indirect evidence suggests that the sensor is present in all cells and is a multi-subunit assembly containing an NAD(P)H oxidase capable of generating peroxide and reactive oxygen intermediates, which serve as signaling molecules. The up-regulation of Epo gene transcription by hypoxia is mediated by at least two known DNA-binding transcription factors, hypoxia-inducible factor 1 (HIF-1) and hepatic nuclear factor 4 (HNF-4), which bind to cognate response elements in a critical 3' enhancer approximately 50 bp in length. HIF-1 binding is induced by hypoxia as well as by cobalt. The activation of HIF-1 by hypoxia depends upon the selective protection of its alpha subunit from ubiquitin-dependent proteolysis by means of a mechanism that involves redox chemistry and perhaps phosphorylation. HNF-4 is an orphan nuclear receptor that is constitutively expressed in kidney and liver and which cooperates with HIF-1 to give maximal hypoxic induction. In hypoxic cells, p300 or a related family member forms a macromolecular assembly with HIF-1 and HNF-4, enabling transduction from the Epo 3' enhancer to the apparatus on the promoter responsible for the initiation of transcription.

Animals↗

PubMed1998

The role of glutamate in physical dependence on opioids.

The present review will evaluate the interactions between kappa-opioid receptors and glutamate within the locus coeruleus (LC) during the development of opioid dependence and on expression of withdrawal from dependence on opioids. Hyperactivity of noradrenergic neurons in the LC has been proposed to play a critical role in the physiological and behavioral responses that comprise opioid withdrawal. Several studies indicate that the excitatory amino acid system, in particular, glutamate and its receptors, participate in both the withdrawal-associated increase in LC neuronal activity and the expression of opioid withdrawal behaviors. Most studies on opioid dependence have focused on the prototypical opioid morphine, which produces its physical dependence through agonist actions at the mu-opioid receptor. Butorphanol (Stadol), which exhibits a markedly different profile of opioid receptor activity than does morphine, produces its physical dependence primarily through actions at the kappa-opioid receptor. Studies from our laboratories using a rodent model in which butorphanol administration induces dependence indicate further that the kappa-opioid receptor is an important regulator of glutamate release within the LC. Glutamate exerts actions within the LC that mediate expression of behavioral symptoms of butorphanol withdrawal.

Analgesics, Opioid↗

PubMed1998

Inorganic polyphosphate in human osteoblast-like cells.

Significant amounts of inorganic polyphosphates and of polyphosphate-degrading exopolyphosphatase activity were detected in human mandibular-derived osteoblast-like cells. The amount of both soluble and insoluble long-chain polyphosphate in unstimulated osteoblast-like cells was higher than in human gingival cells, erythrocytes, peripheral blood mononuclear cells, and human blood plasma. The cellular content of polyphosphate in osteoblast-like cells strongly decreased after a combined treatment of the cells with the stimulators of osteoblast proliferation and differentiation, dexamethasone, beta-glycerophosphate, epidermal growth factor, and ascorbic acid. The amount of soluble long-chain polyphosphate, but not the amount of insoluble long-chain polyphosphate, further decreased after an additional treatment with 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). The decrease in polyphosphate content during treatment with dexamethasone, beta-glycerophosphate, epidermal growth factor, and ascorbic acid was accompanied by a decrease in exopolyphosphatase, pyrophosphatase, and alkaline phosphatase activity. However, additional treatment with 1,25(OH)2D3 resulted in an increase in these enzyme activities. Osteoblast-like cell exopolyphosphatase activity and exopolyphosphatase activity in yeast, rat tissues, and human leukemia cell line HL60 were inhibited by the bisphosphonates etidronate and, to a lesser extent, clodronate and pamidronate. From our results, we assume that inorganic polyphosphate may be involved in modulation of the mineralization process in bone tissue.

Acid Anhydride Hydrolases↗

PubMed1998

[Teratogenic effects of arsenic on rats].

OBJECTIVE: To further clarify the effects of arsenic on pregnant rats, fetuses, fetal cells and to verify the experimental results in vitro, and to study the developmental toxicity and its mechanisms of arsenic in depth. METHODS: Teratogenic methods in vivo combined with scanning electron microscopy and histochemical techniques were used in rats. RESULTS: No apparently toxic symptoms or deaths were observed in rats exposed to various doses of arsenic trioxide of 0, 1, 4 and 10 mg/kg. Fetal death rates in rats were 10.2%, 17.4%, 24.8% and 61.1%, proportions of skeletal deformity were 1.89%, 3.12%, 17.28% and 78.57%, and embryo deformity rates were 3.16%, 5.32%, 13.79% and 40.48% 48 hours after exposure, respectively for those exposed to various doses of arsenic. Damage in fetal epidermal cells and cavities of different size between cell surface and cell junction in multiple sites could be seen under scanning microscope. Dysrhaphia, body anomalies and small limb bud, etc. were main manifestation of embryo deformity. There was a close relationship between nitric oxide and anomalies in fetal development, with a dose-response pattern, showed by inducible nitric oxide synthetase (iNOS) histochemical examinations. In vivo staining showed that excessive apoptosis could be induced by arsenic. And, teratogenic mechanisms of arsenic was analyzed in various ways. CONCLUSION: Arsenic has certain teratogenic effects on rats in vivo.

Animals↗

PubMed1998

[Hepatotoxicity and formation of reactive oxygen species induced by microcystis aeruginosa toxin].

OBJECTIVE: To study hepatotoxicity of Microsystis aeruginosa toxin (microcystin) and its prevention. METHODS: Cytotoxicity and the formation of reactive oxygen species (ROS) of microcystin extracted water bloom were studied in rat liver cells of primary culture. RESULTS: It was found that the release of lactic dehydrogenase (LDH) increased with a time- and dose-dependent pattern in the liver cells treated with microcystin, and a time- dependent formation of ROS also increased simultaneously. The antioxidant, desferrioxamine, could decrease the release of LDH and the formation of ROS in the liver cells treated with microcystin. CONCLUSION: Microcystin has obvious hepatotoxicity and the formation of ROS may play a certain role in its toxic effect on the rat liver cells.

Animals↗

PubMed1998

Long-term Effects of Various Iodine and Fluorine Doses on the Thyroid and Fluorosis in Mice.

OBJECTIVE: To elucidate the participation of the independent and combined long term effect of various concentrations of iodine and fluorine on the pathogenesis of goiter and fluorosis in mice. METHODS: Nine drinking water supplies with different iodine and fluorine content were prepared by combination of potassium iodate and sodium fluoride solutions in bidistilled water. The concentrations of iodide were: 1. iodine deficiency (ID): 0.0; 2. iodine normal (IN): 20.0; 3. iodine excess (IE) 2500.0 ug/l; and these of fluoride were: 1. fluoride deficiency (FD) 0.0; 2. fluoride normal 0.6; 3. fluoride excess (FE), 30.0 mg/l. A total of 288 Kunmim mice was divided into 9 groups consisting of 32 animals each and each group, in addition to basal diet, received one of following iodide/fluoride mixtures: ID+FD, ID+FN, ID+FE, IN+FD, IN+FN, IN+FE, IE+FD, IE+FN, IE+FE. By such manner, one half of the animals of each group was treated for 100 days and the other half for 150 days. RESULTS: It was found that ID only and IE only could both induce the goiter. FE induced dental fluorosis and increased fluorine content in the bone. In addition, fluorine also affected the thyroid changes induced by ID or IE. After 100 days of treatment, fluorine showed some stimulatory effect on the thyroid in ID conditions and inhibitory effect in IE conditions. After 150 days, however, the effects of fluorine on the thyroid reversed as compared with that of 100 days. On the other hand, difference of iodide intake could also increase the toxic effects of FE on the incisors and bones. The rate and degree of the incisor fluorosis, the fluorine contents in the bone were significantly higher in the ID+FE group than those in the IN+FE and IE+FE groups. CONCLUSIONS: Both iodine deficiency and excess induced goiter as well as other functional and histopathological changes in the mouse thyroid. Excessive fluorine caused fluorosis of incisors and limb bones. In addition, iodine and fluorine do have mutually interacting effects on both goiter and fluorosis in the experimental mice.

Journal Article↗

PubMed1998

Microencapsulation of rat islets prolongs xenograft survival in diabetic mice.

OBJECTIVE: To protect the transplanted islets from the host's immune system by means of immunoexclusion membranes. METHODS: Rat islets were isolated from Wistar rat pancreas by ductal collagenase distention, stationary digestion, and finally with the aid of dextran gradient separation. Then the islets were encapsulated in alginate-polylysine-alginate (APA) semipermeable membranes. RESULTS: In vitro studies demonstrated that encapsulated islets secreted insulin in response to glucose challenge for at least 8 weeks, which was similar to free islets. In vivo studies showed that 15 streptozotocin (STZ)-induced diabetic mice were transplanted intraperitoneally with 1000 encapsulated islets without immunosuppression. Diabetes was reversed within 3 days, and the mice remained normoglycemic for up to 160 days, with a mean xenograft survival time of 126 days. The encapsulated islets had a significantly greater effect than unencapsulated islets, which functioned for less than 8 days. CONCLUSIONS: Encapsulation of pancreatic islets in semipermeable membranes can effectively prolong xenograft survival without immunosuppression in an animal model.

Animals↗

PubMed1998

[Three dimensional observation on revascularization and study on bone metabolism of allogenic transplanted mandible].

In order to observe stereological correlation between new vessels and surrounding tissue, 6 rabbits were used for the following experiments. The mandible defect model was made by cutting 1 cm x 0.5 cm bone from both right and left side of mandible. Then, the left defect was repaired by the bone segment from the right side, and the right defect was repaired by frozen allogenic bone segment. One month later, the metabolism of the bone segments was observed by nuclein scintiphotography. The revascularization of the bone segments was observed by vascular corrosion cast method. It was shown that new vessels from host soft tissue could penetrate the periosteum of allogenic transplanted bone, along the absorbing path, ingrowth into the bone. The metabolism of the bone was active. It was suggested that the vessel growth from host to the graft is one of the main patterns of revascularization.

Animals↗

PubMed1998

[Relation between methylmercury chloride-induced programmed cell death and the development of nervous system in rats].

The study was designed to reveal the role of programmed cell death (PCD, or apoptosis) induced by methylmercury chloride (MMC) in SD rat embryos, wish TdT-mediated dUTP nick end labeling (TUNEL), Nile blue sulfate (NBS) vital stailing electron microscopy (SEM) and in vivo teratogenic methods (TEM). Pregnant rats were intraperitoneally injected at gestation day 9.5 with doses of 0, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/kg MMC and killed at 11.5 day later. Results showed that the PCD of embryonic nervous system was apparently dose dependent with MMC during rat head-fold stage. Observations under SEM and TEM showed that MMC caused pathologic changes of epithelia and organellae in embryonic brain such as atrophied or decreased microvilli cavernous damages and mitochondrial swelling and so on. Though MMC could result in developmental anomalies of embryonic brain and other organs, the main defect was open neural tube. The experiment study suggested that over PCD may be one of the teratogenic mechanisms of MMC on rat embryos, developing brain in particular.

Abnormalities, Drug-Induced↗

PubMed1998

[Role of programmed cell death in mediating arsenic-induced rat embryo anomalies].

With a view to further investigating teratogenicity, embryotoxicity and teratogenic mechanism of arsenic on developing embryos, the relationship between apoptosis (programmed cell death, PCD) and arsenic-induced teratogenesis was studied during head-fold stage by using in situ 3'end-labeling of DNA and Nile blue sulfate (NBS) vital staining. Sprague-Dawley rats were intraperitoneally injected on gestation day 9.5 with doses of 0, 1, 4 and 8 mg/kg arsenic respectively, and killed at day 12, the results show that teratogenic incidence and mortality increased to 35.7% and 23.8% respectively, in apparent dose-effect relationship. In NBS staining experience, it was found that arsenic induced PCD in many areas, which related with abnormal development of brain, optic system, somite segmentation, limb bud and so on. In situ 3' end-labeling of DNA further supported above-mentioned results. The positive rate of apoptotic cell death was up to 55.6% (P < 0.05). This research suggested a positive correlation between abnormal PCD and teratogenesis. It may be seen that over-apoptosis is one of teratogenic mechanisms of arsenic. Moreover, our results show that necrosis plays some role in teratogenesis as well.

Abnormalities, Drug-Induced↗

PubMed1998

[The combined effects of MCYST and water organic pollutants on the co-induction of SHE cell transformation and expression of Ras P21 protein].

The authors studied the combined carcinogenic activities of MCYST and organic pollutants in water of Dianshan Lake, using in vitro Syrian hamster embryo (SHE) cell transformation and immunohistochemical assays. The results showed that MCYST alone could not induce SHE cell transformation, but it increased the effects of low dose organic pollutants in cell transformation in a dose-dependent manner. In the cells isolated from type II transformed foci, ras P21 protein showed a positive immunohistochemical staining. It suggests MCYST may be a tumor promoter, which has a synergistic carcinogenic activity organic pollutants in water and the activation of ras oncogene may be one of the factors inducing malignant transformation.

Animals↗

PubMed1998

[The LDL receptor activity of hepatocytes during cholesterol gallstone formation in rabbits].

In order to study the mechanism of cholesterol gallstone formation through rabbit model which was induced by high cholesterol diet, we investigated the LDL receptor activity of hepatocytes binding to 125I-LDL in different phases, namely 1, 2, 3 week group and 4 week, and in a control group besides. In this animal experiment, cholesterol gallstones were induced at 2 week, 3 week and 4 week groups in 4/10, 6/10, and 7/10 cases respectively. The Bmax values of LDL receptor of hepatocytes binding to 125I-LDL decreased significantly in 3 week and 4 week groups (vs 1 week and control groups, P < 0.05). The kd values became increased in 3 week and 4 week groups (vs 1 week and control group, P < 0.05), which suggested that the activity of LDL receptor decreased gradually. In conclusions owing to the intake of high cholesterol diet with the passage of time, the decreased activity of LDL receptor of hepatocytes would reduce the synthesis of bile acid.

Animals↗

PubMed1998

[Influence of arsenic on proliferation and differentiation of rat bud cells in vitro].

The objective of this study was designed to evaluate the developmental toxicity of arsenic and its effect on embryonic chondrogenesis of Sprague-Dawley rat by using Flint's rat limb bud cell micromass cultrure system in vitro. The results revealed that arsenic inhibited markedly both proliferation and differentiation of rat limb bud cells in vitro and there was an obvious dose-response relationship. The concentrations of arsenic for IP50(dose of inhibiting proliferation by 50% of the control value) and ID50(dose of inhibiting differentiation by 50% of the control value) were 0.70 mg/L and 0.21 mg/L respectively. The ratio between IP50 and ID50 was 3.3. These parameters indicated that the influence of arsenic on differentiation of rat limb bud cells was stronger than on proliferation, and arsenic belonged to a strong teratogenic agent and a specific inhibitor. This study suggested that the specific inhibitory action of arsenic on limb bud cell differentiation did not result from the cytotoxicity, but would result from the teratogenic effects of arsenic.

Animals↗

PubMed1998

[Measurement of five cytokines in the serum of malignant lymphoma patients].

OBJECTIVE: To study the clinical significance of serum cytokine levels in patients with malignant lymphoma(ML). METHODS: Serum levels of five cytokines and receptor were measured in 49 patients with ML by RIA and ELISA. RESULTS: Except TNF alpha, significantly higher pretreatment levels of interleukin-2(IL-2), soluble interleukin-2 receptor(sIL-2R), interleukin-6(IL-6) and interleukin-8(IL-8) were observed in most of ML patients at diagnosis or relapse as compared with controls(P < 0.05). Cytokine levels declined in responding patients after therapy and there were no differences between CR cases and controls, the cytokine levels remained elevated in non-responding patients. The levels of IL-2 and sIL-2R correlated with the clinical stage, which were significantly higher in patients in stage III, IV. The increase of sIL-2R correlated with the tumor burden. The level of IL-6 was higher in patients presenting B symptoms and had no correlation with the clinical stage. The elevated IL-8 level correlated with the clinical stage and presenting B symptoms of ML patients and had no correlation with other clinical-hematological parameters. CONCLUSION: The changes of cytokines may be served as a means to observe the condition of ML patients and supervise their response to treatment.

Adolescent↗

PubMed1998

[Myocardial ischemic reperfusion injury affected by the isozymes of nitric oxide synthase and their gene expression: experimental study].

OBJECTIVE: To study nitric oxide (NO), isozymes of NO synthase (NOS) and their gene expression in the isolated working rat heart after ischemia-reperfusion injury. METHODS: We quantified the gene expression of the isozymes of NOS by reverse transcription-polymerase chain reaction (RT-PCR), analyzed the myocardial NOS, malondialdehyde (MDA) content, NO, creatine phosphokinase (CPK) in effluent samples from coronary sinus, and measured the heart function before and after ischemia reperfusion. We also studied the effects of dexamethasone(Dex) and bradykinin(BK) introduced into cardioplegia on myocardial ischemia reperfusion injury. RESULTS: Our study demonstrated that the expression of constitutive NOS(cNOS) mRNA was downregulated and of inducible NOS(iNOS) mRNA upregulated with NO, cNOS decrease and iNOS increase during ischemia reperfusion injury. In Dex-treated group, compared with the control group of ischemia reperfusion, the expression of iNOS mRNA was downregulated, NO and iNOS were reduced, the recovery of myocardial dysfunction was ameliorated and MDA, CPK reduced. In BK-treated group, the expression of NOS mRNA showed no significant change, NO and cNOS were increased. The recovery of myocardial dysfunction was ameliorated. MDA, CPK were also reduced. CONCLUSION: These results indicated that up- and down-regulation of expression of NOS isozymes could be one of the important mechanisms for myocardial ischemic reperfusion injury. Downregulating the expression of iNOS mRNA and activating cNOS could be helpful in myocardial protection.

Animals↗

PubMed1998

[The influence of Kupffer cells on experimental hepatocarcinogenesis].

OBJECTIVE: In order to explore the influence of Kupffer cells on experimental hepatocarcinogenesis. METHODS: A comparative study on the expression of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), ras P21, p53 protein and c-myc gene by means of immunohistochemistry or in situ hybridization during the diethylnitrosamine (DENA)-induced hepatocarcinogenesis performed in rats with and without pretreatment with gadolinium chloride (GC) which might effectively block the activity of Kupffer cells. RESULTS: There was no marked difference in the expression of PCNA and EGF in the liver tissue between the above two groups animals. The positive rate of ras P21 was markedly higher in the GC + DENA group than in the DENA group. The positive rate of p53 protein in GC + DENA group was slightly higher than that of the DENA group, however, the appearance of expression was markedly earlier in the former group (in the 11th and the 19th week respectively). The expression intensity of c-myc gene was markedly higher in GC + DENA group that in DENA group. CONCLUSIONS: The results suggest that Kupffer cells can reduce hepatotoxicity induced by chemical carcinogen, and Kupffer cells may play an inhibitory effect on the process of hepatocarcinogenesis.

Animals↗

PubMed1998

[Clinical study on chanlibao in accelerating second stage of labor].

OBJECTIVE: To find out a new way to strengthen the uterine contraction and shorten the second stage of labor, for improving the prognosis of mother and newborn. METHODS: Primiparae observed were divided into three groups randomly and Chanlibao (CLB, a preparation of Chinese herbal medicine) or oxytocin (OTC) was given to the CLB group (80 cases) and the OTC group (52 cases) respectively, to the third group, as a control group (29 cases) of natural labor, without any drug was given. Time of second stage of labor (TSL) and prognosis of mother and newborn of different groups were observed and compared. And intrauterine pressure (IP) and fetal heart rate were monitored by means of electronic-monitor. RESULTS: TSL and postpartum hemorrhage in the CLB group were less than those in the control group. The average IP in former was higher than that in latter, but with no difference as compared with the OTC group. No side effect of CLB was found. CONCLUSION: CLB could obviously strengthen uterine contraction and shorten the TSL, it is cheap, convenient and with no side-effect, so it is a new safe, effective method for improving prognosis of primiparae and newborn, especially for those nonindicated in using oxytocine or infusion of fluid profusely.

Adult↗