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Biomedical subjects

H Gong

Publications and source records attributed to H Gong.

At least 73 records · Page 4Linked to original sources
PubMed1999

A theoretical basis for investigating ambient air pollution and children's respiratory health.

Acute respiratory health effects in children from exposure at current ambient levels of ozone are well documented; however, evidence for acute effects from other criteria pollutants such as nitrogen dioxide and respirable particles is inconsistent. Whether chronic effects result from long-term exposure to any of these pollutants during childhood is an important unresolved question. Establishing whether acute or chronic effects result from childhood exposure and identifying sensitive subgroups may require integration of biologic mechanisms of lung defenses, injury, and response into the study design and statistical models used in analyses. This review explores the theoretical basis for explaining such adverse effects in light of our contemporary understanding of mechanisms of lung injury and response at the cellular and molecular levels. The rapidly evolving understanding of the effects of air pollution on cellular and molecular levels presents an opportunity to develop and refine innovative biologically based hypotheses about the effects of childhood exposure. We hypothesize that children with low fruit and vegetable intake, low antioxidant levels, high polyunsaturated fat intake, or who have inherited certain alleles for genes involved in lung defenses and immune response regulation may be at increased risk for adverse effects. Because responses to air pollutants of interest are complex and involve a number of pathophysiologic processes, the magnitude of main effects of dietary factors, genes, and gene-environment interactions may be modest for individuals; however, each may make an important contribution to the population burden of preventable respiratory diseases.

Air Pollution↗
PubMed1999

Effects of Na-K-2Cl cotransport regulators on outflow facility in calf and human eyes in vitro.

PURPOSE: Cultured human trabecular meshwork (TM) cells possess substantial Na-K-Cl activity, which is involved in the regulation of TM cell volume. The hypothesis in the present study was that drugs that affect the cotransporter might alter aqueous humor outflow facility (C) in the intact eye. The effects of agents and conditions known to modulate Na-K-CI cotransport activity and/or TM cell volume on C in perfused anterior segments were investigated. METHODS: Human and calf eyes were dissected and perfused, and C was determined according to standard published methods. Perfusates with modified osmolarity were used to cause alterations in TM cell volume. Cl-free perfusate and/or bumetanide (10(-5) M) was used to inhibit Na-K-Cl cotransport activity, and vasopressin (10(-7) M, 10(-8) M) was used to stimulate cotransport activity. RESULTS: In human eyes, hypo-osmotic perfusate decreased C 12%, whereas hyper-osmotic perfusate increased C 44%. These changes lasted approximately 30 minutes, after which C began to normalize. Inhibition of Na-K-Cl cotransport using Cl-free medium or bumetanide resulted in facility increases of 27% and 22%, respectively. There was an additive increase in C with bumetanide plus Cl-free media. Stimulating Na-K-Cl cotransport with 10(-8)M and 10(-7)M vasopressin resulted in 28% and 35% decreases in C, respectively. The results were similar in calf eyes: Cl-free medium or bumetanide resulted in 41% and 52% increases in C, whereas 10(-8) M and 10(-7) M vasopressin resulted in 14% and 19% decreases in C, respectively. CONCLUSIONS: Modulation of Na-K-Cl cotransport results in changes in C that may be mediated in part by cell volume changes.

Aged↗
PubMed1999

[The principles of use of antibiotic drugs in plastic surgery: a preliminary exploration].

OBJECTIVE: To investigate the use of antibiotic drugs in the plastic surgery patients. METHODS: With a random-sampling method, the patterns of use of antibiotic drugs were reviewed in 840 cases (1014 surgical operations) from the Plastic Surgery Hospital, the Chinese Academy of Medical Sciences. RESULTS: About 99.21 per cent of patients received antibiotic drugs, and prophylaxis accounted for about 99.70 per cent of all antibiotic drugs. The drugs used most often for prophylaxis were penicillin, followed by cephalosporins. CONCLUSION: By analysing the data, it is clearly shown that there exist abuse and inappropriate use of antibiotic drugs. Surgeons must keep in mind that antibiotic prophylaxis should be used with appropriate indications, optimum time and duration.

Anti-Bacterial Agents↗
PubMed1999

[Helicobacter pylori infection and expression of PCNA, p53, c-erbB-2 in carcinoma and precancerours lesions of the stomach].

OBJECTIVE: To study the role of Helicobacter pylori (Hp) in gastric carcinoma. METHODS: Hp was examined in 70 patients with gastric carcinoma, 62 patients with pre-malignant lesions and 16 controls by improved Warthin-Starry method and PCNA, p53, cerbB-2 protein examined immunohistochemically. RESULTS: The frequency of Hp infection in gastric carcinoma and its precusor lesions was significantly higher than that in the controls. There was no significant difference in Hp infection rate between gastric carcinoma and its precursor lesions, nor between the intestinal type and diffuse type of gastric carcinoma. Hp infection correlated well with expressions of PCNA, c-erbB-2 and with co-expression of PCNA, p53 and c-erbB-2 in gastric carcinoma and its precusors. p53 protein was expressed only in gastric carcinoma, and its expression level was higher in the presence than in the absence of Hp infection (P < 0.01). CONCLUSION: Hp might act as a tumor promoter in the genesis of gastric cancer.

Helicobacter Infections↗
PubMed1999

[Expression of transforming growth factor alpha and its relationship with HBV infection in hepatocellular carcinomas].

OBJECTIVE: To assess the expression of TGF alpha in hepatocellular carcinoma and its relationship with HBV infection. METHODS: Using in situ hybridization and streptavidin-peroxidase immunohistochemistry to detect TGF alpha mRNA, TGF alpha protein and HBV DNA in 53 cases of HCC and 14 cases of controls. RESULTS: Positive rates of TGF alpha mRNA and TGF alpha protein in carcinoma tissue were 30.2% and 73.6% respectively, which were higher than in normal controls (P < 0.05). The expression of TGF alpha mRNA and TGF alpha protein was increased significantly in dysplastic liver cells (DLC) locating aside from the tumor tissue in comparing with those of non-dysplastic liver cells (NDLC) (P < 0.05). Positive rates of HBV DNA in carcinoma tissue and paratumorous liver tissue were 56.6% and 60.4% respectively, which were higher than in the normal controls (P < 0.001). Positive rate of HBV DNA in the nuclei of tumor tissues, tissue of the dysplastic areas and non-dysplastic areas was lowering down successively (P < 0.05). There was a significant relationship between expression of TGF alpha mRNA and TGF alpha protein in the carcinoma tissues and HBV DNA in the tumorous and its surrounding tissues respectively. CONCLUSIONS: Expression of TGF alpha in carcinoma tissues was closely associated with the existence of HBV DNA and TGF alpha may participate in the early stage of liver carcinogenesis. The increased expression of HBV DNA in nuclei may serve as an important morphology marker in distinguishing carcinoma from DLC and NDLC.

Carcinoma, Hepatocellular↗
PubMed1998

[Preventive and therapeutic effects of calcium lactate on osteoporosis in aged ovariectomized rats].

Twelve-month-old rats were ovariectomized (OVX), remained untreated for one month. Calcium lactate was given daily by gavage at the dose of 125, 250 and 750 mg/kg(Ca125, Ca250, Ca750) for 3 months. The results showed that compared with OVX rats, Ca250 could markedly increase the bone mineral density (BMD) at right femur. Both Ca250 and Ca750 could markedly enhance the ash weight, ratio of ash weight to dry weight of left femur and ratio of 24-hour urinary Ca/Cr. Ca125 could markedly decrease serum ALP concentration. Both Ca125 and Ca250 could decrease the ratio of 24-hour urinary Hop/Cr. All doses of calcium lactate groups could elevate serum Ca, and were no influence on the volume, wet and dry weight of the left femur and serum OC levels. In conclusion, the administration of calcium lactate to aged OVX rats prevents bone resorption, and its mechanism may be relating to the supplement of calcium properly.

Animals↗
PubMed1998

p75NTR and Trk receptors are expressed in reciprocal patterns in a wide variety of non-neural tissues during rat embryonic development, indicating independent receptor functions.

The p75 kDa neurotrophin receptor (p75NTR) has been detected in a number of non-neural tissues, especially during development. Reports of Trk receptor transcripts in non-neural tissues raise the possibility that the sites of p75NTR expression during development may correlate with Trk receptor expression. Coexpression of p75NTR with the Trk receptors in developing non-neural tissues would support the hypothesis that there is a cooperative function between the two receptor subclasses. To address these questions, p75NTR was localized relative to the three known Trk receptors in adjacent sections of rat embryos at stages of development when the highest levels of p75NTR have been observed in the muscle, maxillary pad, kidney, and lung. Using in situ hybridization and immunhistochemical analyses, we show here that the Trk receptors are expressed extensively in non-neural tissues during cell differentiation and tissue morphogenesis but in patterns that are generally reciprocal to that of p75NTR. The results indicate p75NTR most likely functions independently of the Trk receptors in most developing non-neural tissues. However, the p75NTR consistently appears in non-neural cells adjacent to those expressing Trk receptors. The reciprocal patterns of expression indicate that the separate activities of the two receptors most likely complement each other in regulating cell-cell interactions important for the innervation of developing non-neural tissues.

Animals↗
PubMed1998

Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgG1 production.

Leflunomide is an immunosuppressive drug capable of inhibiting T and B cell responses in vivo. A number of studies demonstrate that leflunomide functions both as a pyrimidine synthesis inhibitor and as a tyrosine kinase inhibitor. We previously reported that leflunomide inhibits LPS-stimulated B cell proliferation, cell cycle progression, and IgM secretion. This inhibition can be reversed by the addition of exogenous uridine, suggesting that leflunomide functions as a pyrimidine synthesis inhibitor in B cells. We report here that while the addition of uridine restored proliferation and IgM secretion to leflunomide-treated LPS-stimulated B cells, as determined by metabolic labeling and immunoprecipitation, it did not completely restore secretion of IgG Ab. We hypothesized that leflunomide inhibits LPS-induced IgG secretion by inhibiting tyrosine kinase activity required for isotype switch. We tested this hypothesis in a well-defined model of isotype switch, LPS plus IL-4 induction of IgG1. Leflunomide inhibited IgG1 secretion in this model in a dose-dependent manner. The signal transduction pathway utilized by IL-4 to induce IgG1 involves tyrosine phosphorylation of the IL-4 receptor, JAK1, JAK3, and STAT6 proteins induced by IL-4 binding to the IL-4R. Leflunomide diminished the tyrosine phosphorylation of JAK3 and STAT6 in the absence or presence of uridine. In gel mobility shift studies, STAT6 binding to the STAT6 DNA binding site in the IgG1 promoter decreased in the presence of leflunomide or leflunomide plus uridine. Taken together, these data suggest that leflunomide acts as a tyrosine kinase inhibitor to block IgG1 production.

Animals↗
PubMed1998

In vitro and in vivo mechanisms of action of the antiproliferative and immunosuppressive agent, brequinar sodium.

Intracellular pyrimidine nucleotides (PyN) can be synthesized de novo from glutamine, CO2, and ATP, or they can be salvaged from preformed pyrimidine nucleosides. The antiproliferative and immunosuppressive activities of brequinar sodium (BQR) are thought to be due to the inhibition of the activity of dihydroorotate dehydrogenase, which results in a suppression of de novo pyrimidine synthesis. Here we describe the effects of the pyrimidine nucleoSide, uridine, on the antiproliferative and immunosuppressive activities of BQR. In vitro reduction of PyN levels in Con A-stimulated T cells and inhibition of cell proliferation by low concentrations of BQR (< or =65 microM) are reversed by uridine. However, uridine is unable to reverse the effects of high concentrations of BQR (> or =65 microM). The ability of BQR to induce anemia in BALB/c mice is prevented by the coadministration of uridine. In contrast, the immunosuppressive activity of BQR is unaffected by similar doses of uridine. PyN levels in the bone marrow, but not in the spleen, are depressed in mice treated with BQR. These observations suggest that the induction of anemia by BQR is due to depletion of intracellular PyN in hemopoietic stem cells located in the bone marrow. They also suggest that the mechanism of immunosuppression by BQR may be only marginally dependent on depletion of intracellular PyN in lymphocytes located in the periphery. We report a novel activity of BQR: inhibition of tyrosine phosphorylation, and hypothesize that the immunosuppressive activity may be due, in part, to this unsuspected ability of BQR to inhibit tyrosine phosphorylation in lymphocytes.

Animals↗
PubMed1998

Temperature standardization of multiple spirometers.

In respiratory health surveys involving multiple spirometers, spirometer differences may introduce important biases. We investigated temperature measurement variability as a cause of spirometer differences. Digital thermometers recorded internal (cylinder) and external (outer casing) temperatures of six similar rolling-seal spirometers during field use and in laboratory tests at controlled room temperatures. Internal and external thermometers substantially agreed in recording spirometer temperature changes, which lagged room temperature changes. Offsets of individual thermometers from overall mean readings were roughly the same in field testing of 3908 students in > 60 schools over 5 months and in subsequent laboratory tests. Thermometers differed by as much as 1.3 degrees C, causing differences as large as 0.8% in vital capacity measurements. We conclude that (1) interior and exterior temperatures of typical rolling-seal spirometers do not differ greatly, although both may differ from surrounding air temperature; and (2) variations between individual digital thermometers may be large enough to bias spirometric data appreciably in large-scale surveys. Variations should be controlled by selection of similar-reading thermometers and/or correction to a uniform standard.

Analysis of Variance↗
PubMed1998

Cardiovascular effects of ozone exposure in human volunteers.

We hypothesized that ozone (O3) exposure acutely affects cardiovascular hemodynamics in humans and, in particular, in subjects with essential hypertension. We studied 10 nonmedicated hypertensive and six healthy male adults. Each subject, after catheterization of the right heart and a radial artery, was exposed in an environmentally controlled chamber to filtered air (FA) on one day and to 0.3 ppm O3 on the following day for 3 h with intermittent exercise. Relative to FA exposure, O3 exposure induced no statistically significant changes in cardiac index, ventricular performance, pulmonary artery pressure, pulmonary and systemic vascular resistances, ECG, serum cardiac enzymes, plasma catecholamines and atrial natriuretic factor, and SaO2. The overall results did not indicate major acute cardiovascular effects of O3 in either the hypertensive or the control subjects. However, mean preexposure to postexposure changes were significantly (p < 0.02) larger with O3 than with FA for rate-pressure product (1,353 beats/min/mm Hg) and for heart rate (8 beats/min); these responses were not significantly different between the hypertensive and the control subjects. Significant O3 effects were also observed for mean FEV1 (-6%), and AaPO2 (> 10 mm Hg increase), which were not significantly different between the two groups. These results suggest that O3 exposure can increase myocardial work and impair pulmonary gas exchange to a degree that might be clinically important in persons with significant preexisting cardiovascular impairment, with or without concomitant lung disease.

Adult↗
PubMed1998

[A novel gene delivery system targeting to epidermal growth factor receptor overexpressing cancer cells].

A polypeptide with 33 amino acid residues was designed and synthesized. Its C terminal was composed of multiple lysine residues, which played as a DNA condensing agent, whereas the N terminal was the receptor binding domain of Epidermal Growth Factor(N32-K48). Through a spontaneous self-assembly process with electrostatic interaction, the synthetic peptide combined with a luciferase expression vector, pEBluc, to form an EGF receptor targeting nucleic acid complex. Significant luciferase activity was detected 48 hours after adding this complex directly to the culture medium of the A431 cells. This synthetic peptide could be used to construct a gene transfer system mediated by the endocytosis via EGF receptor. It promoted a very possibility of the gene therapy for the cancers such as glioma, melanoma and squamous carcinoma which are known of epidermal growth factor receptor overexpression.

Carcinoma↗
PubMed1997

Xenopus Cdc6 confers sperm binding competence to oocytes without inducing their maturation.

Amphibian eggs normally require meiotic maturation to be competent for fertilization. A necessary prerequisite for this event is sperm binding, and we show that under normal physiological conditions this property is acquired at, but not before, meiotic maturation. Immature oocytes do not bind sperm, but injection of total egg poly(A)+ mRNA into immature oocytes confers sperm binding in the absence of meiotic maturation. Using an expression cloning approach we have isolated a single cDNA from egg poly(A)+ mRNA that can induce sperm binding in immature oocytes. The cDNA was found to encode Xenopus Cdc6, a protein that previously has been shown to function in initiation of DNA replication and cell cycle control. This unanticipated finding provides evidence of a link between a regulator of the cell cycle and alterations in cell surface properties that affect gamete binding.

Amino Acid Sequence↗
PubMed1997

Xenopus laevis sperm-egg adhesion is regulated by modifications in the sperm receptor and the egg vitelline envelope.

The biochemical and ultrastructural changes in the envelope of the Xenopus laevis egg that occur during oviposition and fertilization have been thoroughly studied (Hedrick, J. L., and Nishihara, D. M., Methods Cell Biol. 36, 231-247, 1991; Larabell, C. A., and Chandler, D. E., J. Electron Microsc. Tech. 17, 294-318, 1991). However, the biological significance of these changes with respect to gamete interaction has been unclear. In the current study, it was found that changes in the envelope are directly responsible for regulating sperm-egg adhesion, an initial step of fertilization. As a result of these transformations, sperm bind only to unfertilized oviposited eggs, not to oocytes or coelomic eggs. In addition, they do not bind to fertilized eggs. The molecular and cellular basis of the regulation of the sperm binding process was investigated in the context of our recent findings that two structurally related envelope glycoproteins, gp69/64, serve as sperm receptors during fertilization (Tian, J.-D., Gong, H., Thomsen, G. H., and Lennarz, W. J., J. Cell Biol. 136, 1099-1108, 1997). Although the purified gp69/64 glycoproteins isolated from the oocyte or coelomic egg envelopes exhibited sperm binding activity, when these proteins are part of the intact oocyte or coelomic egg envelopes, they are not accessible to either anti-gp69/64 antibodies or to sperm. During the conversion from the coelomic to the vitelline envelope, the gp69/64 sperm receptors become exposed on the surface, an event that correlates with proteolytic cleavage of gp43 and accompanying ultrastructural alterations in the envelope. Conversely, after fertilization, when the vitelline envelope of the egg is converted to the fertilization envelope of the zygote, limited proteolytic cleavage of the sperm receptor results in loss of sperm binding activity. In addition, formation of a fertilization layer on top of the structurally altered VE adds another physical block to sperm binding. These results provide new insights into structure-function relationships between envelope components of the anuran egg, and provide further evidence supporting the key role of gp69/64 as sperm receptors during X. laevis fertilization.

Animals↗
PubMed1997

The immunosuppressive metabolite of leflunomide, A77 1726, affects murine T cells through two biochemical mechanisms.

The immunosuppressive metabolite of leflunomide, A77 1726, inhibits the enzymatic activity of protein tyrosine kinases and of dihydro-orotic acid dehydrogenase, an enzyme involved in pyrimidine biosynthesis. Here murine CTLL cell lines were studied to determine which of the biochemical targets of A77 1726 was responsible for the observed inhibition of proliferation and cytotoxic activity. At low concentrations of A77 1726, pyrimidine biosynthesis is the target, since inhibition of proliferation correlates with a reduction in pyrimidine NTP levels and is reversed by uridine. At higher concentrations of A77 1726, uridine no longer reverses the inhibition of proliferation even though pyrimidine NTP levels are restored. This second mechanism for inhibiting proliferation is probably inhibition of protein tyrosine kinases, since these higher concentrations of A77 1726 inhibit IL-2-induced tyrosine phosphorylation of Jak1 and Jak3, the protein tyrosine kinases initiating signaling by the IL-2R. Tyrosine phosphorylation of the beta-chain of the IL-2R, which is required for IL-2-driven proliferation, is also inhibited by A77 1726. Cytotoxicity of a CTLL line that overexpresses the Lck protein tyrosine kinase is inhibited by A77 1726; this inhibition is not affected by uridine, but does correlate with inhibition of an Lck in vitro kinase reaction. These studies establish that inhibition of pyrimidine biosynthesis and that of protein tyrosine kinase both contribute to the effects of A77 1726 on CTLL cell lines.

Aniline Compounds↗
PubMed1997

In vivo mechanism by which leflunomide controls lymphoproliferative and autoimmune disease in MRL/MpJ-lpr/lpr mice.

Two activities have been identified for the immunosuppressive metabolite of leflunomide, A77 1726: inhibition of dihydroorotate dehydrogenase (DHO-DHase), an enzyme involved in the biosynthesis of pyrimidine nucleotides (PyN); and inhibition of protein tyrosine kinases. The in vitro potency of A77 1726 as a DHO-DHase inhibitor is reported to be 10- to 500-fold greater than as a tyrosine kinase inhibitor. These observations suggested that the immunosuppressive efficacy of leflunomide in vivo is related to inhibition of DHO-DHase. However, observations that patients with disorders in the PyN synthetic pathway are not overtly immunodeficient militate against this hypothesis. We investigated the effects of leflunomide in vivo and report that amelioration of lymphoproliferative and autoimmune diseases in MRL/MpJ-lpr/lpr (lpr/lpr) mice by leflunomide is not accompanied by reduced PyN concentrations in lymph node cells. Our hypothesis that lymphocytes could salvage serum uridine to counter the effects of reduced PyN synthesis in vivo was supported by in vitro studies. Finally, we observed that amelioration of disease correlated with a reduction of tyrosine phosphorylated proteins in lymph node cells of lpr/lpr mice. These observations suggest that the primary mechanism by which leflunomide prevents autoimmune and lymphoproliferative diseases in lpr/lpr mice is not depletion of PyN, but correlates with reduced tyrosine phosphorylation concentrations in lymph node cells.

Aniline Compounds↗
PubMed1997

Gamete interactions in Xenopus laevis: identification of sperm binding glycoproteins in the egg vitelline envelope.

A quantitative assay was developed to study the interaction of Xenopus laevis sperm and eggs. Using this assay it was found that sperm bound in approximately equal numbers to the surface of both hemispheres of the unfertilized egg, but not to the surface of the fertilized egg. To understand the molecular basis of sperm binding to the egg vitelline envelope (VE), a competition assay was used and it was found that solubilized total VE proteins inhibited sperm-egg binding in a concentration-dependent manner. Individual VE proteins were then isolated and tested for their ability to inhibit sperm binding. Of the seven proteins in the VE, two related glycoproteins, gp69 and gp64, inhibited sperm-egg binding. Polyclonal antibody was prepared that specifically recognized gp69 and gp64. This gp69/64 specific antibody bound to the VE surface and blocked sperm binding, as well as fertilization. Moreover, agarose beads coated with gp69/64 showed high sperm binding activity, while beads coated with other VE proteins bound few sperm. Treatment of unfertilized eggs with crude collagenase resulted in proteolytic modification of only the gp69/64 components of the VE, and this modification abolished sperm-egg binding. Small glycopeptides generated by Pronase digestion of gp69/64 also inhibited sperm-egg binding and this inhibition was abolished by treatment of the glycopeptides with periodate. Based on these observations, we conclude that the gp69/64 glycoproteins in the egg vitelline envelope mediate sperm-egg binding, an initial step in Xenopus fertilization, and that the oligosaccharide chains of these glycoproteins may play a critical role in this process.

Amidohydrolases↗