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Biomedical subjects

P Ye

Publications and source records attributed to P Ye.

At least 55 records · Page 3Linked to original sources
PubMed1998

Production and testing of Schistosoma japonicum candidate vaccine antigens in the natural ovine host.

The objectives of this work were to clone and express Chinese strain Schistosoma japonicum antigens and evaluate their immunogenicity and protective efficacy in the natural ovine host in China. Recombinant antigens selected for testing were: isoforms of glutathione S-transferase Sj28GST and Sj26GST; the large hydrophilic domain of Sj23, the homologue of the protective S. mansoni membrane antigen Sm23; and a 3' fragment of S. japonicum paramyosin. In addition, Chinese strain S. japonicum native paramyosin and GST were purified and used for vaccination. Antigens were co-administered with Freund's adjuvants or BCG. We also examined the effects of co-administration of native unfractionated GSTs with keyhole limpet haemocyanin (KLH), which shares a cross-reactive protective epitope with schistosomes. These are the first side-by-side comparisons of candidate defined-antigen schistosomiasis vaccines in a natural host. Significant partial protection was obtained with each of the antigens tested. Less protection was obtained with a recombinant fragment of S. japonicum paramyosin compared with native paramyosin. Co-administration of native GST and KLH was no more effective than vaccination with either antigen alone. Although encouraging levels of protection against S. japonicum were demonstrated using each of these antigens, further work is needed to optimise vaccine delivery and vaccination schedules.

Adjuvants, Immunologic↗
PubMed1998

Antitumor activity with the HSV-tk-gene-modified cell line PA-1-STK in malignant mesothelioma.

Malignant mesothelioma (MM) is a thoracic malignancy that is increasing in incidence. Since it is uniformly fatal and kills by local spread, investigators have proposed that MM is a good target for novel treatment approaches, such as gene therapy. We hypothesized that delivery of the HSV-tk gene, using gene-modified tumor cells (PA-1-STK cells), would result in an antitumor effect after treatment with ganciclovir. In in vitro mixing experiments, we found that PA-1-STK cells killed both mouse and human mesothelioma cells in a dose-dependent manner. Moreover, we found that PA-1-STK cells also prolonged survival of mice with MM when the percentage of total tumor cells was high (70%), but observed no survival benefit when the percentage of PA-1-STK cells was low (30%). These data support the rationale for a cell-based gene therapy approach to MM.

Animals↗
PubMed1998

Insulin-like growth factor I (IGF-I) regulates IGF binding protein-5 gene expression in the brain.

Insulin-like growth factor (IGF-I) plays an important role during brain development. IGF binding protein-5 (IGFBP-5) is known to be capable of modulating IGF-I actions and is expressed in brain during development. To begin to investigate the interaction between IGF-I and IGFBP-5 in brain, we asked whether IGF-I influences the brain expression of IGFBP-5. We quantified IGFBP-5 expression in multiple brain regions of two lines of IGF-I transgenic (Tg) mice that exhibit distinctive patterns of brain transgene expression. MT-I/IGF-I Tg mice carry a transgene driven by metallothionein-I (MT-I) promoter and exhibit highest levels of transgene expression in cerebral cortex, whereas in IGF-II/IGF-I Tg mice the mouse IGF-II promoter drives the transgene and the expression is highest in the cerebellum. In normal adult mice, IGFBP-5 messenger RNA (mRNA) was detected in all brain regions examined, and the highest levels of the mRNA were found in cerebellum, followed by brainstem, diencephalon, hippocampus, and cerebral cortex. Compared to these littermate controls, IGFBP-5 mRNA abundance was increased in both lines of Tg mice. In MT-I/IGF-I Tg mice, cerebral cortex had the greatest increase (approximately 200%), whereas cerebella of IGF-II/IGF-I Tg mice had the greatest increase in IGFBP-5 mRNA (approximately 350%). The increase in IGFBP-5 mRNA correlated with the regional expression of the transgene during development. The abundance of IGFBP-5 protein was also found to be increased in both IGF-I Tg mouse lines. The influence of IGF-I on IGFBP-5 expression was specific because we found no evidence of changes in IGFBP-2, IGFBP-4, or cyclophilin expression. Furthermore, as judged by in situ hybridization histochemistry, IGF-I appeared to increase both the number of IGFBP-5-expressing cells and the magnitude of their expression, an observation that was especially marked in the molecular layer and white matter of the cerebellum. These data indicate that IGF-I regulates IGFBP-5 expression in vivo and is consistent with the in situ hybridization data of others showing that IGFBP-5 expression is temporally and spatially related to that of IGF-I.

Animals↗
PubMed1998

[Expression of Epstein-Barr virus membrane antigen in CHO cell].

A recombinant plasmid, pCMV/MA, was generated by isolating the Epstein-Barr Virus(EBV) membrane antigen(MA) gene with anchor sequence removed from pSV40/MA and cloning it into pcDNA3, with MA gene and Neomycin gene under the control of CMV promoter and SV40 promoter respectively. CHO cells were transfected with pCMV/MA using liposome and then grown in DMEM medium in the presence of G418. Two clones highly expressing MA were obtained. EBV-MA was purified from the medium of CHO cells by ammonium sulfate precipitation. Western-blot showed that the molecular weight of proteins expressed were about 340 kD and 220 kD. It could specifically react with anti-MA monoclonal antibody in indirect immunofluorescent and immunodot assay. The yield of MA was estimated to be 1.9 micrograms/ml per day by SDS-PAGE scanning and Lowry methods. The optimal culture condition of the CHO cells was to use medium supplemented with 10% serum until 80% cell confluence, then with 2%-5% serum and collected medium continually. The genetic stability of the cells was confirmed by freeze--revival and culture without G418. The purified MA was used to immunize mice and the geometric mean titer of the specific antibody was 1:180, while the positive rate of antibody was 100%.

Animals↗
PubMed1998

[Collagen sponge and its hemostatic properties].

Soluble collagen was extracted from bovine tendon in acid solution. Collagen sponge hemostatics were prepared by means of lyophibization. The amino acid and UV spectrum analyses were made to confirm the composition of the soluble collagen. The results of experiments on rabbits indicated the collagen sponge prepared in the authors' lab had excellent hemostatic and adhesive properties in vivo surgical tests.

Amino Acids↗
PubMed1998

Adenoviral-mediated interferon-gamma gene therapy augments pulmonary host defense of ethanol-treated rats.

Alcohol has long been recognized as an immunosuppressive drug and a risk factor for a spectrum of infectious diseases. Among these infections, bacterial pneumonias are most closely correlated with alcohol abuse. One potential mechanism of ethanol-induced immunosuppression is through its ability to suppress alveolar macrophage production of tumor necrosis factor (TNF-alpha). This defect can be reversed by priming macrophages with interferon-gamma (IFN-gamma). We hypothesized that macrophage priming in vivo in a model of acute ethanol intoxication could augment pulmonary host defenses. To test this hypothesis, we used adenoviral-mediated gene transfer of the IFN-gamma gene. This strategy resulted in prolonged expression of IFN-gamma in vivo. Moreover, in a model of acute ethanol intoxication, this vector significantly enhanced lipopolysaccharide-induced TNF-alpha responses and lung polymorphonuclear leukocyte recruitment. Furthermore, pulmonary host defenses against Klebsiella pneumoniae were significantly augmented. These enhanced host defenses were not reversed with pretreatment with a polyclonal anti-TNF-alpha antibody, suggesting that IFN-gamma's effect was through a non-TNF-alpha-dependent mechanism. These data demonstrate that ethanol-induced suppression of pulmonary host defenses can be reversed with IFN-gamma gene therapy.

Adenoviridae↗
PubMed1998

Gene therapy for malignant mesothelioma: a novel approach for an incurable cancer with increased incidence in Louisiana.

Malignant mesothelioma (MM) is a tumor of the pleura for which there is no satisfactory treatment. It is an almost universally fatal disease, regardless of the stage of the tumor at the time of diagnosis. Current treatment modalities include surgery, chemotherapy, and radiation therapy, although in some series none of these modalities is superior to no treatment at all. Because of the dismal prognosis for patients with MM, new modes of treatment are desperately needed. A promising area of research into the treatment of various malignancies is gene therapy. Recent studies have demonstrated the utility of exposing tumor cells to cells transduced to express the Herpes simplex virus gene for thymidine kinase (HSV-TK). By virtue of their expression of HSV-TK, the transduced cells are rendered susceptible to the antiviral drug, ganciclovir (GCV). Nearby untransduced tumor cells are killed by a so-called bystander effect. We are describing a Phase I clinical gene therapy trial for MM, which we are presently conducting at the Louisiana State University Medical Center of New Orleans. The purpose is to study the safety and to determine the maximal tolerated dose of an HSV-TK-transduced ovarian cancer cell line (PA1-STK cells) that is infused into the pleural cavities of patients. This infusion is followed by systemic administration of GCV. The hope is that administration of GCV will result in killing of both the transduced ovarian cancer cells as well as the nearby malignant cells.

Ganciclovir↗
PubMed1997

Regulation of insulin-like growth factor I (IGF-I) gene expression in brain of transgenic mice expressing an IGF-I-luciferase fusion gene.

Insulin-like growth factor I (IGF-I) plays an important role in the development and function of the central nervous system (CNS). Little is known, however, about the factors and mechanisms involved in regulation of CNS IGF-I gene expression. To facilitate our goal to define mechanisms of IGF-I gene regulation in the CNS, we generated several lines of transgenic (Tg) mice that express firefly luciferase (LUC) under control of a 11.3-kb fragment from the 5' region of the rat IGF-I gene. Consistent with expression of the native IGF-I gene in murine brain, expression of the transgene predominated in neurons and astrocytes and used promoter 1, the major IGF-I promoter in the CNS and in most tissues. Transgene messenger RNA and protein expression rapidly increased after birth and peaked at postnatal (P) day 4 in all brain regions studied. LUC activities in all regions then gradually decreased to 0.5-4% of their peak values at P31, except for the olfactory bulb, which maintained about one third of its maximal activity. Compared with littermate controls, administration of dexamethasone decreased LUC activity and transgenic IGF-I messenger RNA abundance, whereas GH significantly increased the expression of the transgene. Addition of GH to cultured fetal brain cells from Tg mice for 12 h also increased LUC activity in a dose-dependent manner (77-388%). These results show that this IGF-I promoter transgene is expressed in a fashion similar to the endogenous IGF-I gene, and thus indicates that the transgene contains cis-elements essential for developmental, GH, and glucocorticoid regulation of IGF-I gene expression in the CNS. These Tg mice should serve as an useful model to study mechanisms of IGF-I gene regulation in the brain.

Aging↗
PubMed1997

[Accumulation and excretion of fluorine and effect of selenium on them in rats with chronic fluorosis].

2 groups of Wistar rats with chronic fluorosis were duplicated with 30 and 50 mg/L fluorine (F) in drinking water. 2. 0 mg/kg selenium (Se) in fodder was supplemented in the other 2 groups of rats with fluorosis. The amount of drinking water and diet, the excretion of urine and the contents of urine F were tendentiously surveyed every month in one year and then, intake and excretion of F were calculated per day. The contents of Se in urine, liver and serum and F in bone, liver, kidney and serum were measured in the 4th, 8th, and 14th month. The results showed that F absorption increased and F excretion/F absorption rate decreased in 2 groups of rats with fluorosis compared with control group and there were positive correlations between concentration of urine F and water F, as well as concentration of F urine and time of drinking F water. The accumulation of F in bone and liver occurred in the middle period of fluorosis and then, the increase of serum F was observed in the late period of fluorosis in 2 groups of rats with fluorosis. After supplement of Se, urine, liver and serum Se ascended. At the same time, state of eating and drinking improved, the weight rose and the amount of urine excretion heightened, as well as there was an increase of urine F and excretion F/absorption F rate and there was a decrease of bone, live, kidney and serum F in rat of Se supplementation with fluorosis compared with non-Se groups.

Animals↗
PubMed1997

Repair of incomplete simple syndactyly by a web flap on a subcutaneous tissue pedicle.

A new web flap on a subcutaneous tissue pedicle was developed to repair incomplete simple syndactyly. It was isolated from the top skin in syndactyly and transferred down into the depth of the web space to create a web commissure. With use of this technique, aesthetic appearance of the web and well-functioning fingers were gained. Moreover, this technique made full use of the original skin of the syndactyly, and a skin graft was not needed. We report here the operative technique, which presents another alternative for repair of incomplete simple syndactyly.

Adolescent↗
PubMed1996

In vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development in transgenic mice: evidence that IGF-I increases proliferation of granule cell progenitors.

The in vivo actions of insulin-like growth factor-I (IGF-I) on cerebellum development have been investigated in transgenic (Tg) mice (IGF-II/I Tg mice) in whom an IGF-II promoter-driven IGF-I transgene is highly expressed in cerebellum. Compared to normal littermates, the brains of IGF-II/I Tg mice exhibited overgrowth beginning from the second week of postnatal life. Among the brain regions examined, cerebellum exhibited the greatest increase in size, such that by 50 days of age cerebellar weight and DNA content were increased by 90% and 143%, respectively, compared to littermate controls. Morphological studies of adult IGF-II/I Tg mice showed that the total number of granule and Purkinje cells was increased by 82% and 20%, respectively, findings consistent with the increased cerebellar DNA content and indicating that the increased cerebellar weight was due in part to an increase in cell number. The thickness of the molecular layer also was increased in IGF-II/I Tg mice. During early postnatal development the number of external granular layer cells, as well as the number of BrdU labeled external granular cells, was increased. These data strongly indicate that IGF-I increases granule cell number by a mechanism that involves the stimulation of granule cell progenitor proliferation. Our findings also indicate that IGF-I influences the growth of Purkinje cells and possibly of other cell types in the cerebellum.

Animals↗
PubMed1996

The role of the insulin-like growth factors in the central nervous system.

Increasing evidence strongly supports a role for insulin-like growth factor-I (IGF-I) in central nervous system (CNS) development. IGF-I, IGF-II, the type IIGF receptor (the cell surface tyrosine kinase receptor that mediates IGF signals), and some IGF binding proteins (IGFBPs; secreted proteins that modulate IGF actions) are expressed in many regions of the CNS beginning in utero. The expression pattern of IGF system proteins during brain growth suggests highly regulated and developmentally timed IGF actions on specific neural cell populations. IGF-I expression is predominantly in neurons and, in many brain regions, peaks in a fashion temporally coincident with periods in development when neuron progenitor proliferation and/or neuritic outgrowth occurs. In contrast, IGF-II expression is confined mainly to cells of mesenchymal and neural crest origin. While expression of type I IGF receptors appears ubiquitous, that of IGFBPs is characterized by regional and developmental specificity, and often occurs coordinately with peaks of IGF expression. In vitro IGF-I has been shown to stimulate the proliferation of neuron progenitors and/or the survival of neurons and oligodendrocytes, and in some cultured neurons, to stimulate function. Transgenic (Tg) mice that overexpress IGF-I in the brain exhibit postnatal brain overgrowth without anatomic abnormality (20-85% increases in weight, depending on the magnitude of expression). In contrast, Tg mice that exhibit ectopic brain expression of IGFBP-1, an inhibitor of IGF action when present in molar excess, manifest postnatal brain growth retardation, and mice with ablated IGF-I gene expression, accomplished by homologous recombination, have brains that are 60% of normal size as adults. Taken together, these in vivo studies indicate that IGF-I can influence the development of most, if not all, brain regions, and suggest that the cerebral cortex and cerebellum are especially sensitive to IGF-I actions. IGF-I's growth-promoting in vivo actions result from its capacity to increase neuron number, at least in certain populations, and from its potent stimulation of myelination. These IGF-I actions, taken together with its neuroprotective effects following CNS and peripheral nerve injury, suggest that it may be of therapeutic benefit in a wide variety of disorders affecting the nervous system.

Animals↗
PubMed1996

Use of transgenic mice for understanding the physiology of insulin-like growth factors.

Manipulation of the murine genome, either by the insertion of transgenes or by disruption of native genes (so-called gene knockout, accomplished by homologous recombination), and study of the resultant mutant mice have proved invaluable to our understanding of insulin-like growth factor (IGF) physiology. Such investigations have demonstrated that expression of both IGF-I and IGF-II is essential to normal in utero growth of the fetus, while IGF-II is required for normal placental growth. IGF-I is necessary for normal in utero maturation and postnatal growth. Data from study of type 1 IGF receptor (IGF 1R) knockout mice indicate that this receptor mediates most IGF-I and IGF-II growth-promoting actions. The central importance of the IGFs and the IGF 1R to development is underscored by the fact that IGF 1R knockout mice do not survive past birth. Our more recent studies of transgenic mice have begun to demonstrate IGF-I actions in brain, such as the stimulation of myelination and the augmentation of neurone survival.

Animals↗
PubMed1996

In vivo effects of insulin-like growth factor-I on the development of sensory pathways: analysis of the primary somatic sensory cortex (S1) of transgenic mice.

In the rodent brain, insulin-like growth factor I (IGF-I) messenger RNA is transiently expressed in sensory projection neurons during periods of synaptogenesis and neuronal growth. Transgenic (Tg) mice with brain IGF-I overexpression and ectopic brain expression of IGF-binding protein-1 (IGFBP-1), an inhibitor of IGF-I actions, show changes in brain size and myelination. We used these mouse models to evaluate in vivo IGF-I effects on sensory pathway development by conducting anatomical studies in the S1 barrel field. Brain size, cortical area, and barrel field dimensions were increased in IGF-I and reduced in IGFBP-1 Tg mice compared with those in wild-type (wt) mice. The brain and cerebral cortex of Tg mice with the highest transgene expression were the most altered in size. Cortex and barrel field size changes were not precisely proportional, because in some Tg mice barrels were relatively more affected than the cortex, whereas in others the opposite was observed. Brain IGF-I overexpression increased the average number of neurons per barrel, neuronal cell body cross-sectional area, and barrel neuropil volume, whereas brain expression of IGFBP-1 reduced each. Neuronal density was greatly reduced in IGF-I Tg mice and increased in IGFBP-1 Tg mice. No differences in body weight, whisker pad and follicle areas, and whisker pad innervation density were found among Tg and wt mice. These observations indicate that IGF-I enhances neuronal growth in developing sensory pathways and support the concept that modified availability of local trophic factors, such as IGF-I, changes brain, neocortical, and S1 relative dimensions by altering neuronal survival and neuropil elaboration. Study of the S1 cortex provides an excellent model to probe the in vivo mechanisms of IGF actions.

Animals↗
PubMed1996

Polymorphisms of the human lipoprotein lipase gene: possible association with lipid levels in patients with coronary heart disease in Beijing area.

The polymorphisms (Pvu II and Hind III) on the lipoprotein lipase (LPL) gene locus was investigated in a sample of 100 patients surviving previous myocardial infarction and 100 age matched healthy individuals selected from Han Chinese of Beijing area. In patient group a strong association was found between H+ allele of Hind III polymorphism and raised TG levels (P < 0.01). In control group P-P- genotype was observed to be associated with higher TG levels compared with P+P genotype of Pvu II polymorphism (P < 0.05). Combination of H+H+ genotype with P-P- genotype showed the highest TG levels among all nine kinds of genotypic combinations in patient group (P < 0.01). However, comparison of distribution of alleles and genotypes of these polymorphisms between patient group and control group demonstrated no significant difference. Our data suggest that the polymorphisms at the LPL gene, as the linkage markers with an aetiologic mutation at or around LPL gene, may constitute one of the genetic determinants for the population variation in plasma TG levels, as well as for the common dyslipidemia in Chinese populations.

Aged↗
PubMed1995

Insulin-like growth factor-I influences the initiation of myelination: studies of the anterior commissure of transgenic mice.

The effects of insulin-like growth factor-I (IGF-I) on the initiation of myelination have been examined in the posterior portion of anterior commissure of the transgenic (Tg) mice that overexpress IGF-I in brain, and those which exhibit ectopic brain expression of IGF binding protein-1 (IGFBP-1), an inhibitor of IGF actions. In IGF-I Tg mice the number of ensheathed axons was increased compared to their normal littermates. The distribution of the axon size further showed that both small (< 300 nm) and large (> 700 nm) axons were more often ensheathed and myelinated. The opposite was true in IGFBP-1 Tg mice. These data indicate that IGF-I increases myelin ensheathment independent of axon diameter, and support the hypothesis that the absolute axon size is not the sole determinant for the initiation of myelination in CNS.

Age Factors↗