Biomedical subjects

B Xu

Publications and source records attributed to B Xu.

At least 199 records · Page 11Linked to original sources

PubMed1998

Viral and nonviral gene delivery vectors for cancer gene therapy.

The development of vectors that are capable of efficient gene delivery is crucial to the success of gene therapy. We have developed both recombinant viral and nonviral vectors with the goal of correcting genetic abnormalities in cancer cells that are responsible for malignant transformation. Infection of cancer cells by recombinant adenovirus (Adv) indicates that the level of transduction is variable and dependent on the virus-to-cell ratio. Infection of cells with Adv/p53 resulted in levels of tumor suppressor p53 gene expression that could mediate tumor cell growth suppression and apoptosis, both in vitro and in vivo. The treatment of cancer cells with cisplatin prior to Adv transduction resulted in a higher level of therapeutic gene expression. Epidermal growth factor (EGF)/DNA complexes targeted to cancer cells overexpressing the EGF receptor resulted in efficient transduction of several lung cancer cell lines in vitro. As a result, these vectors provide improved methods with which to treat cancer in the clinical setting with gene therapy.

Adenoviridae↗

PubMed1998

Interleukin-12 enhances contact hypersensitivity by modulating the in vivo cytokine pattern in mice.

It has been proven that interleukin-12 (IL-12) can modify Th1 and Th2 cell-mediated immune diseases by altering the development and cytokine production of the cells. In this study, we investigated the in vivo immunomodulatory effect of recombinant murine IL-12 on contact hypersensitivity, a Th1 cell-mediated disease. For this purpose, Balb/C mice were sensitized with 3% 4-ethyoxymethylene-2-phenyl-oxazol-5-one (OXAZ), and recombinant mouse IL-12 was given simultaneously during the induction phase. Contact allergy was then elicited by ear challenge with 1% OXAZ. We examined the mouse ear swelling response, in vivo cytokine gene expression in the skin and local lymph nodes, and in vitro cytokine production by the spleen lymphocytes. It was found that in vivo IL-12 treatment during the induction phase significantly enhanced the ear swelling response to OXAZ in sensitized mice. Moreover, remarkable mononuclear cell infiltration and edema and higher expression of Th1 cytokine mRNAs (IL-2 and interferon-gamma) in the skin lesion and local lymph nodes were observed in contact allergic mice with IL-12 treatment compared with contact allergic mice without IL-12 treatment. The expression of Th2 cytokine mRNA (IL-4) in the skin lesion and local lymph nodes, however, was largely downregulated, with no change in IL-5 mRNA in IL-12-treated contact allergic mice. We found, unexpectedly, that, similar to the effects on phytohemagglutinin (PHA) stimulated in vitro IL-2 and IFN-gamma production, PHA-induced in vitro IL-4 production was enhanced in the spleen lymphocytes from IL-12-treated contact allergic mice. Our results indicate that exogenous IL-12 enhanced contact hypersensitivity probably because of the in vivo promoting and suppressing effects of IL-12 on Th1 and Th2 gene expression, respectively.

Animals↗

PubMed1998

Expression of interleukin-18 in murine contact hypersensitivity.

In this study, we made a mouse model for contact hypersensitivity (CH) using oxazolone as a contact allergen and examined the expression of interleukin-18 (IL-18) in the diseased skin sites at both mRNA and protein levels. In the kinetic study by semiquantitative RT-PCR, IL-18 mRNA was constitutively produced in normal murine skin but increased significantly at 12 h and peaked at 24 h in the ear skin of CH mice. A positive correlation was confirmed between the IL-18 mRNA signal and CH, as measured by mouse ear swelling response. Histologically, in situ hybridization showed that the IL-18 mRNA signal was weakly observed in the dermis but not the epidermis of normal skin, whereas the IL-18 mRNA signal was found intensively in the dermis, particularly in inflammatory cell areas. Using IL-18-specific antibody immunostaining, it was further found that IL-18 protein production had a histologic location similar to that of IL-18 mRNA in both normal and CH mice. The present study suggests that IL-18 may be implicated in the pathogenesis of murine CH.

Animals↗

PubMed1998

Tissue-specific effects of in vivo adenosine receptor blockade on glucose uptake in Zucker rats.

Previous studies have shown that treatment of obese Zucker rats with the adenosine receptor antagonist 1,3-dipropyl-8-(p-acrylic) phenyl xanthine (BWA1433) improves intraperitoneal glucose tolerance. In this study, a euglycemic hyperinsulinemic clamp was performed on obese (fa/fa) and lean (Fa/fa) Zucker rats that had been treated orally with BWA1433 or vehicle for 1 wk. A constant infusion of [3H]glucose was initiated in fasted animals to measure basal whole body glucose kinetics. No differences in glucose concentration or rates of glucose production/disappearance were observed between lean or obese animals with or without BWA1433. During the euglycemic hyperinsulinemic clamp, whole body glucose disposal in obese Zucker rats was only 22% of that observed in lean animals. BWA1433 treatment increased glucose disposal by 88% in obese Zucker rats. At the end of the clamp, [14C]-2-deoxyglucose was injected to determine tissue-specific differences in glucose uptake. Gastrocnemius, soleus, heart, and liver of untreated obese animals had significantly lower glucose uptake than lean controls under hyperinsulinemic conditions. BWA1433 treatment of obese animals increased glucose uptake in gastrocnemius and soleus muscles by 44 and 47%, respectively. Conversely, BWA1433 treatment decreased glucose uptake in adipose tissue by 54 and 49% in obese and lean Zucker rats, respectively. In summary, BWA1433 improves glucose tolerance by increasing glucose uptake in skeletal muscle while decreasing glucose uptake by adipose tissue. This study suggests that insulin resistance in obese Zucker rats is tissue specific and that signaling from adenosine receptors may be a factor contributing to tissue-specific insulin resistance.

Adipose Tissue↗

PubMed1998

A virus-encoded RNA polymerase purified from baculovirus-infected cells.

A DNA-dependent RNA polymerase was purified to homogeneity, starting from insect cells infected with the baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). The purified polymerase supported accurate and specific transcription from late and very late promoters but was not active on viral early promoters. Thus, promoter recognition is an integral function of the purified enzyme. The purified RNA polymerase was composed of only four equimolar subunits, which makes it the simplest DNA-directed RNA polymerase from a eukaryotic source described so far. Amino-terminal protein sequencing, peptide fingerprinting, and immunochemical analyses were used to identify the four subunits, all of which are virus encoded. Overexpression of the four viral proteins (LEF-8, LEF-4, LEF-9, and p47) in baculovirus-infected cells resulted in a significant increase in the levels of RNA polymerase produced in the infected cells. Thus, the overexpression data are consistent with our identification of the RNA polymerase subunits.

Amino Acid Sequence↗

PubMed1998

A1 adenosine receptor antagonism improves glucose tolerance in Zucker rats.

The A1 adenosine receptor (A1ar) antagonist 1,3-dipropyl-8-(p-acrylic)-phenylxanthine (BW-1433) was administered to lean and obese Zucker rats to probe the influence of endogenously activated A1ars on whole body energy metabolism. The drug induced a transient increase in lipolysis as indicated by a rise in serum glycerol in obese rats. The disappearance of the response by day 7 of chronic studies was accompanied by an increase in A1ar numbers. Glucose tolerance tests were administered to rats treated with BW-1433. Peak serum insulin levels and areas under glucose curves (AUGs) were 34 and 41% lower in treated obese animals than in controls, respectively, and 19 and 39% lower in lean animals. With chronic administration (6 wk), AUGs decreased 47 and 33% in obese and lean animals, respectively. There was no effect of BW-1433 in either lean or obese rats on weight gain or percent body fat. Thus the major sustained influence of whole body A1ar antagonism in both lean and obese animals was an increase in whole body glucose tolerance at lower levels of insulin.

Adipocytes↗

PubMed1998

NO modulates P-selectin and ICAM-1 mRNA expression and hemodynamic alterations in hepatic I/R.

The anti-inflammatory role of nitric oxide (NO) was studied in a model of hepatic ischemia-reperfusion (I/R) in rats. Male Fischer rats were subjected to 30 min of no-flow ischemia of the left and median lobes of the liver, and animals were examined for a 4-h period of reperfusion. The animals were divided into the following groups: control-vehicle; I/R-vehicle; I/R-Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv, 10 min before reperfusion); sham control-L-NAME, and I/R-S-nitroso-N-acetyl-penicillamine (SNAP, 25 micromol/kg iv, 10 min before reperfusion, followed by 20 micromol. kg-1. h-1 in 1.0 ml saline infused for 4 h). Results showed that mean arterial blood pressure was significantly increased in the sham control-L-NAME or I/R-L-NAME groups compared with either the I/R-vehicle or I/R-SNAP groups. However, cardiac index (CI) and stroke volume index (SVI) were markedly decreased, and systemic vascular resistance index (SVRI) was dramatically increased. Interestingly, the CI and SVI in rats treated with SNAP were markedly improved over that of the I/R group. Plasma nitrate and nitrite levels were significantly decreased in the I/R-L-NAME group; however, superoxide generation in the ischemic lobes and plasma alanine aminotransferase activity were higher compared with I/R-SNAP rats. The L-NAME-induced enhancement of hepatic injury in rats with I/R may be due in part to neutrophil infiltration, which was significantly increased compared with animals subjected to I/R or I/R-SNAP. The mechanism of L-NAME-enhanced neutrophil infiltration may be due to the fact that the ratios of P-selectin and intercellular adhesion molecule 1 (ICAM-1) mRNA to glyceraldehyde-3-phosphate dehydrogenase mRNA extracted from the ischemic lobes of I/R-L-NAME rats were significantly increased when compared with the I/R-SNAP group. These results suggest that 1) endogenous NO reduces the SVRI and permits an increased CI and SVI; 2) exogenous NO further improves CI and SVI; and 3) endogenous, but not exogenous, NO decreases P-selectin and ICAM-1 mRNA expression, thereby reducing polymorphonuclear neutrophil-dependent reperfusion tissue injury.

Alanine Transaminase↗

PubMed1998

Anorectic effects of the cytokine, ciliary neurotropic factor, are mediated by hypothalamic neuropeptide Y: comparison with leptin.

Although ciliary neurotropic factor (CNTF) is a tropic factor in nervous system development and maintenance, peripheral administration of this cytokine also causes severe anorexia and weight loss. The neural mechanism(s) mediating the loss of appetite is not known. As hypothalamic neuropeptide Y (NPY) is a potent orexigenic signal, we tested the hypothesis that CNTF may adversely affect NPYergic signaling in the hypothalamus. Intraperitoneal administration of CNTF (250 microg/kg) daily for 4 days significantly suppressed 24-h food intake in a time-dependent manner and decreased body weight. The loss in body weight was similar to that which occurred in pair-fed (PF) rats. As expected, hypothalamic NPY gene expression, determined by measurement of steady state prepro-NPY messenger RNA by ribonuclease protection assay, significantly increased in PF rats in response to energy imbalance. However, despite a similar loss in body weight, there was no increase in NPY gene expression in CNTF-treated rats. Daily administration of CNTF intracerebroventricularly (0.5 or 5.0 microg/rat) also produced anorexia and body weight loss. In this experiment, negative energy balance produced by both PF and food deprivation augmented hypothalamic NPY gene expression. However, despite reduced intake and loss of body weight, no similar increment in hypothalamic NPY gene expression was observed in CNTF-treated rats. In fact, in rats treated with higher doses of CNTF (5.0 microg/rat), NPY gene expression was reduced below the levels seen in control, freely fed rats. Furthermore, CNTF treatment also markedly decreased NPY-induced feeding. These results suggested that anorexia in CNTF-treated rats may be due to a deficit in NPY supply and possibly in the release and suppression of NPY-induced feeding. The possibility that CNTF-induced anorexia may be caused by increased leptin was next examined. Daily intracerebroventricular injections of leptin (7 microg/rat) decreased food intake, body weight, and hypothalamic NPY gene expression in a manner similar to that seen after CNTF treatment. Leptin administration also suppressed NPY-induced feeding. However, peripheral and central CNTF injections markedly decreased leptin messenger RNA in lipocytes, indicating a deficiency of leptin in these rats; thus, leptin was unlikely to be involved in appetite suppression. Thus, these results show that a two-pronged central action of CNTF, causing diminution in both NPY availability and the NPY-induced feeding response, may underlie the severe anorexia. Further, unlike other members of the cytokine family, suppression of NPYergic signaling in the hypothalamus by CNTF does not involve up-regulation of leptin, but may involve a direct action on hypothalamic NPY neurons or on neural circuits that regulate NPY signaling in the hypothalamus.

Adipocytes↗

PubMed1998

Glial reactivity and impaired glutamate metabolism in short-term experimental diabetic retinopathy. Penn State Retina Research Group.

The early pathophysiology of diabetic retinopathy and the involvement of neural and vascular malfunction are poorly understood. Glial cells provide structural and metabolic support for retinal neurons and blood vessels, and the cells become reactive in certain injury states. We therefore used the streptozotocin rat model of short-term diabetic retinopathy to study glial reactivity and other glial functions in the retina in the first months after onset of diabetes. With a two-site enzyme-linked immunosorbent assay, we measured the expression of the intermediate filament glial fibrillary acidic protein (GFAP). After 1 month, GFAP was largely unchanged, but within 3 months of the beginning of diabetes, it was markedly induced, by fivefold (P < 0.04). Immunohistochemical staining showed that the GFAP induction occurred both in astrocytes and in Müller cells. Consistent with a glial cell malfunction, the ability of retinas to convert glutamate into glutamine, assayed chromatographically with an isotopic method, was reduced in diabetic rats to 65% of controls (P < 0.01). Furthermore, retinal glutamate, as determined by luminometry, increased by 1.6-fold (P < 0.04) after 3 months of diabetes. Taken together, these findings indicate that glial reactivity and altered glial glutamate metabolism are early pathogenic events that may lead to elevated retinal glutamate during diabetes. These data are the first demonstration of a specific defect in glial cell metabolism in the retina during diabetes. These findings suggest a novel understanding of the mechanism of neural degeneration in the retina during diabetes, involving early and possibly persistent glutamate excitotoxicity.

Acute Disease↗

PubMed1998

Catalase transfection decreases hydrogen peroxide toxicity in a pancreatic beta cell line.

BetaTC6-F7 cells like normal Beta cells were found to be highly sensitive to hydrogen peroxide and to possess very low levels of catalase. Therefore we tested whether overexpression of catalase could enhance resistance to hydrogen peroxide. Enzyme activity was increased forty fold by transient transfection of a catalase transgene. To assess protection from hydrogen peroxide a cotransfection method using a human growth hormone reporter gene was developed. Human growth hormone secretion was shown to be a suitable marker for insulin secretion since both hormones demonstrated virtually identical glucose dose response curves. Catalase transfection was found to provide significant protection against hydrogen peroxide indicating that low catalase may contribute to the sensitivity of cells to hydrogen peroxide.

Animals↗

PubMed1998

The effect of thyrotropin receptor antibodies on the proliferation of FRTL-5 cells and the expression of protooncogene c-fos mRNA.

OBJECTIVE: Hyperthyroidism and a diffuse goiter are the main symptoms of Graves' disease (GD) associated with autoantibodies to thyroid-stimulating hormone (TSH) receptor (TRAb). The present study was conducted to evaluate effects of autoantibodies in patients with GD (TRAb-IgG) on induction of the proliferation and c-fos mRNA expression in FRTL-5 cells (Fisher rat thyroid cell line). METHODS: Highly purified IgG fractions were isolated from 11 patients with GD, TRAb-IgG and 15 normal individuals (normal controls) with Protein A Sepharose CL-4B affinity column chromatograph. FRTL-5 cells, which had been grown to subconfluency and deprived of TSH for a few days. Then, these cells were used for measuring cAMP content, 3H-thymidine incorporation in cells and the expression of c-fos mRNA respectively. RESULTS: After stimulation of TRAb-IgG, the cAMP production and 3H-thymidine incorporation in FRTL-5 cells were much higher than those from normal controls (P < 0.05 respectively). Using 32P labelled v-fos probe by the Northern Blot method, the expression of c-fos mRNA could be induced by IgGs from patients with GD. CONCLUSIONS: These data suggest that the stimulation of TRAb-IgG followed by cAMP production and 3H-thymidine incorporation is related to the induction of c-fos mRNA and, thus, to the growth of FRTL-5 cells.

Animals↗

PubMed1998

Effects of verapamil on down-regulation of norepinephrine-induced beta adrenoceptors in cultured rat cardiomyocytes.

AIM: To determine whether verapamil (Ver) inhibits norepinephrine (NE)-induced beta adrenoceptors down-regulation in cultured rat cardiomyocytes. METHODS: [3H]-Dihydroalprenolol (DHA) radiobinding assay was used to measure beta adrenoceptor density, fluorescent indicator Fura 2-AM was used to estimate levels of free cytosolic calcium ([Ca2+]i). RESULTS: Ver reduced [Ca2+]i and increased beta adrenoceptor density, NE increased [Ca2+]i and reduced beta adrenoceptor density of cultured cardiomyocytes, these effects were time and concentration dependent. Ver inhibited the above effects of NE. CONCLUSIONS: Ver increased beta adrenoceptor density and inhibited NE-induced beta adrenoceptor down-regulation of cardiomyocytes.

Adrenergic alpha-Agonists↗

PubMed1998

[A longitudinal study on growth model and velocity of term small for gestation age].

To probe into the vegetal pattern and find out the key period of promoting normal growth of term small for gestational age (TSGA), a longitudinal study on growth model and velocity of TSGA was conducted from Jan 1993 to June 1997. The body weight and length of 150 children of TSGA (57 boys, 93 girls) and 152 children as controls (58 boys, 94 girls) were measured from the 1st month to 36th month. The growth model was analysed by multilevel models. The result showed that there was a difference between the growth models of TSGA and controls. During 8 and a half months (center month), the weight, length of controls were 1.19 kg, 3.46 cm greater than those of TSGA; the weight, length of boys were 0.34 kg, 1.08 cm more than those of girls respectively. The growth velocity of TSGA was similar to that of controls. The maximal growth velocity was observed during the first 6 monthes after birth. The order of growth velocity from high to low was 1 mo. > 2 mo. > 3 mo. in length and weight, showing that children of TSGA have their own growth model. Their growth velocity should be monitored attentively. If low velocity appears one should search for the cause and adopt apropriate measures to ensure their growth in accordance with their "own track".

Body Height↗

PubMed1998

Coronary angiographic characteristics in unstable angina pectoris.

OBJECTIVE: To investigate the angiographic characteristics of coronary lesions in patients of different subgroups of unstable angina pectoris. METHODS: Coronary angiograms and clinical manifestations were analysed on 388 patients. RESULTS: Single-vessel disease was more common in new onset effort angina (69.64%) than in other subgroups (P < 0.05); triple-vessel disease and left main coronary artery disease appeared more frequently in patients with rest angina than in other subgroups (72.34% and 27.66% respectively, P < 0.05), so did complex lesions and type C lesions (36.07% and 60.64% respectively, P < 0.05). More than half of the culprit lesions in post-infarction angina were subtotal or total occlusions (53.12%), being more frequently found in this than in other subgroups (P < 0.05). Most of the patients with Prinzmetal variant angina had mild coronary lesions only. Coronary thrombi were found in 10.45% of the 388 patients; they were more frequent in patients with post-infarction angina (20.00%) than in the subgroups of new onset effort angina, aggravated effort angina and Prinzmetal variant angina (4.26%, 7.53% and 0% respectively, P < 0.05). Coronary thrombi were also more frequent in patients with chest pain at rest (16.39%) than in the subgroups of new onset effort angina and Prinzmetal variant angina (P < 0.05). CONCLUSIONS: It is suggested that patients with angina at rest should be treated more intensively. Energetic anticoagulation treatment should be given to patients with post-infarction angina and angina at rest.

Adult↗

PubMed1998

[Retrospective analysis of 18 cases with agranulocytosis induced by antithyroid drugs].

OBJECTIVE: To analyse the routine WBC count's effect on predicting antithyroid drugs-induced agranulocytosis developing and risk factors of antithyroid drugs-induced agranulocytosis. METHODS: Retrospective analysis of 18 Graves' cases with agranulocytosis induced by antithyroid drugs during 1984-1995. RESULTS AND CONCLUSIONS: Most of antithyroid drugs-induced agranulocytosis happens 2-12 weeks after the administration of antithyroid drug, and are related with the drug's doses. Some agranulocytosis happens abruptly, routine WBC and granulocyte count can not predict some agranulocytosis developing. Fever and throat sore are the intitial symptoms of agranulocytosis, if it happens, the WBC and granulocyte count must be checked immediately. The treatment of granulocyte-macrophage colony stimulating factor is effective, the corticosteroid therapy seems not to be useful for the recovery of granulocyte count.

Adult↗

PubMed1998

[The study on treatment of Chinese children's Class II malocclusion by Herbst appliance].

OBJECTIVE: To study the effects of early treatment for chinese children with class II malocclusion. METHODS: 30 chinese children were treated by Herbst appliance. The cephalometric analysis were used to evaluate the effects of early treatment. RESULTS: Herbst appliance can restrict the growth of maxilla and stimulate the growth of mandible, at the same time, the appliance leads to the retroclining of upper incisors, proclining of lower incisors and mesial movement of lower molars. CONCLUSION: Herbst appliance can achieve remarkable effects of growth modification for chinese children's class II malocclusion.

Adolescent↗

PubMed1998

[Effect of recombinant human growth hormone with total parenteral nutrition on albumin synthesis in patients with peritoneal sepsis].

OBJECTIVE: To investigate the effect of recombinant human growth hormone (rhGH) in combination with total parenteral nutrition (TPN) on albumin synthesis in patients with peritoneal sepsis. METHOD: 17 patients with peritoneal sepsis were divided randomly into two groups. The control group received TPN only for 7 days, and the GH group received both rhGH (12 U/d) and TPN for 7 days. The TPN scheme and other treatment were the same in the two groups. RESULT: Serum albumin, prealbumin, and transferrin concentration were increased in patients in the GH group (P < 0.01), but no apparent effect was observed in the control group (P > 0.05). CONCLUSION: In condition of serious peritoneal sepsis, TPN can not increase albumin, prealbumin, and transferrin synthesis alone, whereas rhGH in combination with TPN significantly increase the synthesis of visceral proteins.

Adolescent↗

PubMed1998

[Hard nucleus cataract extraction by phacoemulsification with intraocular lens implantation].

OBJECTIVE: To investigate the technique of phacoemulsification for hard nucleus cataract extraction and evaluate its therapeutic effects. METHODS: Three methods of phacoemulsification, the improved divide and conquer, the reserve lens cortex spin and no lens cortex spin, were performed on 62 eyes according to the type of nucleus hardness. RESULTS: With foldable or 5.5 mm PMMA intraocular lens implantation, the improved divide and conquer phacoemulsification was performed on 26 eyes, the reserve lens cortex spin phacoemulsification on 23 eyes and no cortex spin phacoemulsification on 13 eyes. At postoperative 3 days, 5 days and 30 days, the visual acuities without correction 0.5 or better were obtained respectively in 46 eyes (74.2%), 60 eyes (96.8%) and 61 eyes (98.4%). The major complications were corneal edema and posterior capsular rupture. CONCLUSION: The technique of phacoemulsification for hard nucleus cataract is worthy to be spread due to safety, easiness and minimum complication.

Aged↗