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Biomedical subjects

X Xing

Publications and source records attributed to X Xing.

At least 55 records · Page 3Linked to original sources

Safety study and characterization of E1A-liposome complex gene-delivery protocol in an ovarian cancer model.

A phase I clinical trial of E1A-liposome complex is currently ongoing in patients with HER-2/neu-overexpressing breast or ovarian cancers. To optimize the E1A-liposome complex for a further stage of clinical trial, several aspects of the current protocol have been examined in an animal model. In the orthotopic ovarian cancer model, different doses of lipid in the the E1A-liposome complex, which is currently used in clinical trials, were tested for the in vivo gene-transfer efficacy and tumor-suppression function. A lowered lipid dose--1/13 of the previous amount--produced gene expression level and E1A tumor-suppression efficacy similar to that of the original protocol. Mini-E1A, an E1A construct without its immortalization domain and yet capable of repressing HER-2/neu, was proved to be as potent as E1A in suppressing tumor development in vivo. These changes in the E1A-liposome complex will significantly reduce any potential adverse effects caused by lipid vector and E1A DNA. To examine further whether residual E1A DNA may still exist in normal organs after the E1A-liposome treatment, PCR was used to detect E1A DNA in mice that survived for 1 1/2 years after the last treatment. E1A DNA was detected only in the lungs and kidneys, but not in livers, hearts, spleens, brains, uterus or the ovaries. Furthermore, resistance of the E1A DNA extracted from tissues to the digestion of Dpnl restriction enzyme, which can cleave the methylated E1A plasmid DNA generated by methylation-competent bacteria, suggested integration of E1A DNA into the chromosome of the lungs and kidneys. Experimental results presented here provide important information for safety concerns and for the design of future phase II and phase III trials.

Adenovirus E1A Proteins↗

[Clinical application of photodynamic therapy combined with non-coherent light (red light) for treatment of port-wine stains].

OBJECTIVE: This is to report the clinical application of photodynamic therapy (PDT) combined with non-coherent light (red light) for the treatment of port wine stains (PWS). METHODS: Eleven cases with PWS have been treated with PDT combined with non-coherent light since Dec. 1995. RESULTS: The facial lesions of PWS in the 11 cases disappeared completely without any scarring. CONCLUSION: PDT combined with red light that has strong skin-penetrating ability and irradiation just after intravenous injection of photosensitizing drugs are effective to embolize the malformative vasculature in pink lesions, especially in dark purple lesions and purple lesions with proliferation.

Adolescent↗

[The effect of palate repair on middle ear function].

By means of acoustic impedance and otoscopic examinations the middle ear function and incidence of secretory otitis media (SOM) were demonstrated in 43 cases of cleft palate children pre- and post palatal closure. The results showed that 61.36% of the 86 ears had SOM prior to palatal closure and there was no difference between cleft types (P > 0.05). The patient with the age of 9 years or less have higher incidence of SOM than the older ones (P < 0.05). The study indicated that the middle ear status can be improved by palatal surgery for the cleft palate children.

Adolescent↗

[Ultrasound bone measurement of the tibia: comparison with vertebral dual-energy X-ray absorptiometry and appendicular single photon absorptiometry].

OBJECTIVE: Ultrasonic techniques have been used to assess the mechanical properties of bone. Recently, a new ultrasonic bone instrument, which measured the SOS (speed of sound) at the tibial shaft, has been introduced (Sound Scan 2000, Myriad Ultrasound Systems Ltd.). The aim of this work was to investigate the correlation of tibial SOS with bone mineral density (BMD). METHODS: The tibial SOS was measured in 213 healthy women (aged 22-83 years) and 56 female primary osteoporosis with vertebral fractures (aged 53-82 years). Values of SOS were compared with BMD assessed by dual energy x-ray absorptiometry (DEXA) at spine and hip sites and single photon absorptiometry (SPA) at the distal forearm. RESULTS: Tibial SOS correlated more closely with the BMD of lumbar, hip and forearm (r = 0.387-0.928, P < 0.001). The tibia SOS values and the BMD values measured by the DEXA and SPA were negatively correlated to age and years since menopause. In particular, they were obviously lower in the group of 50 years old. The tibial SOS of vertebral fracture group was significantly lower than that of well-matched non-fracture-group (n = 104, aged 51-84 years). CONCLUSIONS: Tibial SOS was significantly correlated with BMD measured by DEXA or SPA respectively and able to discriminate patients with vertebral fracture from the age-matched controls.

Absorptiometry, Photon↗

[Preserving remnant liver function after major hepatic vein occlusion].

OBJECTIVE: To observe the pathological changes of the remained hepatic lobe after major hepatic vein (MHV) occlusion. METHOD: Seventy-eight rats were randomly divided into the control group, the ligation group of segmental hepatic vein, the stricture group of left MHV, and the ligation group of left MHV. The pathology, hepatic microcirculation and hemodynamic changes of the involved hepatic lobe of MHV occlusion were dynamically determined. RESULT: Necrosis occurred in the hepatocytes at the first postoperative day in the ligation group of MHV. Extensive collaterals between the hepatic veins and the portal veins appeared in the periphery of involved liver lobe in the stricture group of MHV. The levels of endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of portal vein obviously increased in the ligation group of MHV and also increased in the stricture group of MHV. The levels of endotoxin and TXB(2)/6-Keto-PGF1alpha in the blood of portal vein in the ligation and stricture group of MHV were apparently higher than those in the ligation group of segmental hepatic vein and in the control group. CONCLUSION: The involved liver tissue can not tolerate complete MHV occlusion. The hepatic tissue lacking of MHV drain not only loss its function, but also cause endotoxemia and disorder of hepatic microcirculation. The involved hepatic lobe after the MHV ligation should have been resected at the same time.

6-Ketoprostaglandin F1 alpha↗

LDL oxidation by activated monocytes: characterization of the oxidized LDL and requirement for transition metal ions.

Monocytes can be activated by incubation with opsonized zymosan (Zop), and under these conditions can oxidize low density lipoprotein (LDL). We have characterized the biochemical changes in the lipoprotein after this oxidation. We found that monocyte-oxidized LDL has increased mobility on agarose gels, increased absorbance at 234 nm, increased content of lysophosphatidylcholine, and fluorescence at 430 nm when excited at 350 nm. All these features were somewhat less pronounced in monocyte-oxidized LDL than in LDL oxidized by 5 micrometer CuSO4. Under appropriate conditions, Zop-stimulated monocytes oxidized LDL to a form recognized by macrophage scavenger receptors. Monocytes stimulated by Zop produced superoxide and also oxidized LDL, whereas monocytes stimulated by phorbol ester produced slightly more superoxide but did not oxidize LDL. We found that the chelators EDTA and diethylenetriaminepentaacetic acid inhibited LDL oxidation by Zop-stimulated monocytes, implying a requirement for transition metal ions. We found that Zop contained approximately 5 nmol iron per mg, probably as Fe3+. Zop stripped of its iron supported superoxide production by monocytes, but did not support LDL oxidation. Furthermore, Fe2+ appeared in the medium when monocytes were incubated with Zop, but not with iron-stripped Zop. Taken together, these results imply that monocytes stimulated by Zop are able to oxidize LDL only because of contaminating iron in the commercial zymosan preparations. and requirement for transition metal ions.

Cells, Cultured↗

Analysis of a temperature-sensitive vaccinia virus mutant in the viral mRNA capping enzyme isolated by clustered charge-to-alanine mutagenesis and transient dominant selection.

We have previously reported the successful development of a targeted genetic method for the creation of temperature-sensitive vaccinia virus mutants [D. E. Hassett and R. C. Condit (1994) Proc. Natl. Acad. Sci. USA 91, 4554-4558]. This method has now been applied to the large subunit of the multifunctional vaccinia virus capping enzyme, encoded by gene D1R. Ten clustered charge-to-alanine mutations were created in a cloned copy of D1R. Four of these mutations were successfully transferred into the viral genome using transient dominant selection, and each of these four mutations yielded viruses with plaque phenotypes different from that of wild-type virus. Two of the mutant viruses, 516 and 793, were temperature sensitive in a plaque assay. Mutant 793 was also temperature sensitive in a one-step growth experiment. Phenotypic characterization of the 793 virus under both permissive and nonpermissive conditions revealed nearly normal patterns of viral protein and mRNA synthesis. Under nonpermissive conditions the 793 virus was defective in telomere resolution and blocked at an intermediate stage of viral morphogenesis. In vitro assays of various capping enzyme activities revealed that in permeabilized virions, enzyme guanylylate intermediate formation was reduced and methyltransferase activity was thermolabile, while in solubilized virion extracts enzyme guanylylate activity was reduced and both guanylyltransferase and methyltransferase activities were absent. Thus, the 793 mutation affects at least two separate enzymatic activities of the capping enzyme, guanylyltransferase and methyltransferase, and when incorporated into the virus genome, the mutation yields a virus that is temperature sensitive for growth, telomere resolution, and virion morphogenesis.

Alanine↗

Safety studies of the intraperitoneal injection of E1A--liposome complex in mice.

The HER-2/neu (also called c-erbB-2) proto-oncogene is overexpressed in many human cancer cells, including those of breast cancer and ovarian cancer. We have previously shown that adenovirus 5 E1A inhibits HER-2/neu transcription and functions as a tumor suppressor gene in HER-2/neu-overexpressing cancer cells. Liposome-mediated E1A gene transfer suppresses tumor development and prolongs survival of tumor-bearing mice. In support of a phase I clinical trial of an E1A-liposome complex administered to patients with HER-2/neu-overexpressing breast of ovarian cancer, we conducted a series of studies to evaluate the safety of intraperitoneal injection of E1A in normal mice. The cumulative doses used were from five to 40 times the DNA-lipid starting dose proposed for the phase I clinical trial. In this dosing range, the administration of the E1A-liposome complex had no adverse effects on renal, hepatic and hematological parameters studied. No major organ pathologic changes were observed. We concluded that intraperitoneal administration of E1A-liposome complex at the proposed dose would not be expected to produce significant toxicity. The E1A-liposome clinical trial was recently approved by the Recombinant DNA Advisory Committee and Food and Drug Administration for a phase I trial in patients with HER-2/neu-overexpressing breast and ovarian cancer.

Adenoviridae↗

[Diagnosis and treatment of hepatic tuberculoma].

OBJECTIVE: To explore the appropriate diagnosis and treatment for hepatic tuberculoma. METHOD: Eight cases with hepatic tuberculoma confirmed pathologically were reported and analyzed. RESULTS: Five of the eight cases were misdiagnosed as other types of hepatic tumor, and only 3 cases correctly diagnosed preoperatively. All cases underwent segmentectomy or local resection, and no relapse was found after four-year follow-up in seven cases. CONCLUSIONS: The cases with hepatic occupying-space lesions who had tuberculosis history should be suspected of being hepatic tuberculoma; The aspiration liver biopsy guided by B-mode ultrasound and CT scan can provide correct diagnosis; The segmentectomy and local resection are effective and practicable for treatment of hepatic tuberculoma, and the antituberculosis drugs should be administrated postoperatively so as to strengthen the therapeutic effect.

Adult↗

[Studies on the antimould activity of compound TBZ and its application in paint].

The compound TBZ is a new antimould agent, which contains mainly [2-(4-thiazolyl) benzoimidazole (TBZ)], ethanoic acid and propionic acid. It was shown in laboratory experiment that the compound TBZ had excellent mycostatic effect on all the 10 fungi tested with 70% of the mycostatic zones larger than 6.0 cm. It had obvious inhibitary activity on Alternaria Nees and Aureobasidium Pullulans isolated from mouldy wall. In laboratory condition the surface of fibreboard painted with compound TBZ did not become mouldy in 120 days, while the 20% of that coated with TBZ directly mixed in the paint became mouldy. In practical use, the antimould effect of the wall painted with compound TBZ could maintain more than two years.

Alternaria↗

[The frequencies of the vitamin D receptor gene alleles in adults of Han nationality in Beijing area].

Vitamin D receptor (VDR) gene is considered as one of candidate genes related to the genetic basis of bone and mineral metabolism. In order to determine VDR genotypes, we analysed the polymorphisms, or genotypes of Bsm I, Apa I, and Taq I restriction enzymes, by PCR technique in 223 unrelated healthy adults of Han nationality in Beijing area. Some of the VDR genotypes were also confirmed by Southern blotting analysis. We discovered that Chinese had high frequencies of b, a, T alleles, as high as 95%, 75%, and 95% respectively, which were different from those in Caucasians and Japanese, but similar to those in Koreans (P > 0.05). This difference gave us further insight into the different pathogeny of osteoporosis in various ethnics.

Adult↗

[The association between vitamin D receptor gene polymorphisms, bone mineral density and osteocalcin in Chinese women].

OBJECTIVE: To investigate the correlations between vitamin D receptor (VDR) gene polymorphisms, and bone mineral density (BMD) as well as osteocalcin. METHODS: We used PCR-RFLP and Southern hybridization analysis to determine VDR genotypes in 202 Chinese women. BMD was measured by dual-energy X-ray absorptiometry (DEXA) and serum osteocalcin level was determined by radioimmunoassay. Analysis of covariance was used to test differences in mean BMDs across genotypes. RESULTS: We realized that VDR genotype frequencies in Chinese women were apparently different from those of Caucasians. In group of postmenopausal women, "bb" or "aa" genotype was related to lower BMD in Femoral Neck and Trochanter. No association was found between VDR genotypes and the serum osteocalcin level. CONCLUSION: There was some association between VDR genotypes and BMD in Chinese women. Its function in predicting osteoporosis still requires further study.

Adult↗

Polymorphisms of vitamin D receptor gene and its association with bone mineral density and osteocalcin in Chinese.

OBJECTIVE: To explore the distribution frequencies of vitamin D receptor (VDR) gene polymorphisms in Chinese and the relationship between VDR genotypes and bone mineral density (BMD) or serum osteocalcin level in Chinese women. METHODS: Polymorphisms of VDR gene were analyzed by polymerase chain reaction (PCR) to amplify the DNA sequence and three restriction enzymes (namely BsmI, ApaI and TaqI) to digest the PCR products in 223 subjects. Some of the VDR genotypes were also confirmed by Southern hybridization analysis. BMD was measured at the spine and proximal femur by dual-energy X-ray absorptiometry (DEXA). Serum osteocalcin concentrations were determined by radioimmunoassay. RESULTS: Chinese had high frequencies of "b,a,T" alleles, 95%, 75% and 95% respectively, which were much different from Caucasians. "BB" or "AA" genotype had tendency for higher BMD at some sites in the group of young women, whereas in the group of postmenopausal women, "bb" or "aa" genotype had relationship with lower BMD at femoral neck and trochanter. Furthermore, no relationship were found between VDR genotypes and the serum osteocalcin level in Chinese women. CONCLUSIONS: Allele frequencies of VDR gene in Chinese are different from those in Caucasians. VDR gene polymorphisms are associated with BMD in Chinese, but in a different pattern from other reports. Further study on predicting function of VDR for osteoporosis is necessary.

Adult↗

[Influence of reperfusion following ischemia on microvessels and microcirculation of skeletal muscle].

In order to study the influence of reperfusion following ischemia on microvesseles and microcirculation of skeletal muscle, unilateral hindlimbs of 16 rabbits were subjected to normothermic ischemia for 2 and 5 hours by tourniquet. After release of the tourniquet, microcirculation of the peritenon on dorsum of the foot was observed for 1 hours by intravital microscope. At 1 hour and 72 hours following reperfusion, the anterior tibia muscle biopsiy were taken and the specimens were subjected to light and electron microscopic examinations. It was found that after release of the tourniquet, in the limbs undergone 2 hours ischemia, there was immediate and well distributed reflow in the microvesseles of peritenon though a few aggregates of red cells and increase in the number of adherent leukocytes occured in some venules, and the microvesseles of the skeletal muscle only showed signs of minimal injury, the muscle fibers could survive in the limbs undergone 5 hours of ischemia, however, there was serious disturbance of microcirculation in the peritenon, which was characterized by "no reflow" in most area and there was significant increase in the number of leukocytes adherent to venular endothelium, and the microvesseles of the skeletal muscle showed signs of severe injury, including remarkable swelling of the endothelial cell, disruption of the basement membrane and interstitial edema, and finally, most of the muscle fibers had necrosis occured. The results demonstrated that reperfusion following ischimia might result in microvascular injury and microcirculation disorder in the ischemic area. The degree of the injury and disorder depended on the duration of ischemic period, and was an important factor which determined the fate of the parenchymal cell.

Animals↗

Reproducibility of nutrient intake in a food frequency questionnaire used in a general population.

This study evaluates the reproducibility of nutrient intake in a 45-item food frequency questionnaire (FFQ). The FFQ was mailed in 1980 to persons eligible to participate in a large cohort study on diet and cancer risk; a follow-up version with 75 food items was mailed in 1988 to selected original participants. A random sample of 500 men and 500 women from the New York State general population was selected from individuals who responded to both waves of the study. The subjects' 1988 responses were compared with their original 1980 responses; Pearson's correlations ranged from 0.25 for retinol to 0.55 for vitamin C with or without supplements and vitamin E with supplements in women. Reproducibility of nutrient intake in this questionnaire indicates that brief FFQs may be a useful tool to study nutrient intake and chronic disease relationships, although they are subject to substantial measurement error and dietary change.

Adolescent↗