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Biomedical subjects

X Xing

Publications and source records attributed to X Xing.

At least 19 recordsLinked to original sources

Normal changes in spinal bone mineral density in a Chinese population: assessment by quantitative computed tomography and dual-energy X-ray absorptiometry.

This study was designed to determine age- and gender-based normative values for spinal bone mineral density (BMD) in a Chinese population. In addition, we compared our data with those of other countries and populations. Four hundred and forty-three healthy Chinese subjects, aged 10-79 years (189 males, mean age 46.9 years; 254 females, mean age 45.7 years) were recruited for BMD assessment. BMD was measured by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA), including posteroanterior DXA (PA-DXA), lateral DXA (L-DXA) and midlateral DXA (mL-DXA). For both genders, BMD values peaked in the 10-19 year age group when measured by QCT, and in the 30-39 year age group when measured by PA-DXA. BMD values decreased with age after reaching peak bone density in males and females for all measurements, except for PA-DXA in males. Male BMD values by DXA tended to increase beginning with the 60-69 age group through the 70-79 age group whether by PA-DXA, or L-DXA and mL-DXA. However, male QCT data showed stable BMD values among these two older groups. Comparative results showed female QCT data were higher in the 20-39 age group and lower after the 40-49 age group compared with American females. The peak BMD value by PA-DXA in Chinese females was reached in the same age group as American and European females and was similar in magnitude (p > 0.05). However, the peak BMD value for Chinese females was reached earlier and was significantly higher than that observed in Japanese females (p < 0.001). We conclude that the age group in which the peak BMD values are reached is different depending on the technique used, as is the calculated age-related rate of bone loss. It can be speculated that such differences reflect different timing for bone maturation in cancellous and cortical bone.

Absorptiometry, Photon

DNA ligase gene disruptions can depress viral growth and replication in poxvirus-infected cells.

Poxvirus-encoded DNA ligases are assumed to play a role in viral DNA replication; however mutational inactivation of vaccinia ligase has not been reported to affect viral growth rates in culture. This communication re-examines this surprising aspect of poxviral biology using both Shope fibroma virus (SFV) and vaccinia virus. SFV and vaccinia ligase deficiencies create essentially identical phenotypes. In particular, ligase-deficient SFV strains are mildly UV sensitive and etoposide resistant, phenotypes previously shown to characterize ligase-deficient vaccinia strains. Moreover, we find that ligase mutations can inhibit the growth of both SFV and vaccinia virus in vitro. The poor growth observed in the absence of a viral ligase is correlated with a two- to tenfold reduction in viral and extragenomic DNA synthesis. This phenotype is host dependent. No differences in viral growth or DNA yield were seen when vaccinia strains were cultured on rabbit (SIRC) cells, but ligase deficiencies reduced growth and DNA yields when vaccinia was plated on BSC-40 cells or SFV on SIRC cells. Despite these replicative defects, mutational inactivation of SFV ligase produced no detectable increase in the number of viral DNA breaks and had no effect on virus-catalyzed extragenomic DNA recombination or UV repair. We conclude that poxviral ligases do play a role in viral DNA replication, but the replicative defect is obscured in some cell lines.

Animals

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

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

Identification of a specific DNA region required for enhanced transcription of HER2/neu in the MDA-MB453 breast cancer cell line.

Overexpression and/or amplification of the HER2/neu gene has been shown in roughly 30% of breast cancer patients. Increased levels of HER2/neu mRNA in some breast cancer cell lines is partially caused by increased gene transcription. In MDA-MB453 human breast cancer cells, an activated trans-acting factor is involved in the increased transcription of HER2/neu by mediating its effects through a specific DNA region in the HER2/neu promoter. A methylation interference experiment showed a novel sequence for protein-DNA interactions. Three polypeptides of approximately 110, 70, and 35 kD interact with this DNA element. This region of the human HER2/neu promoter is highly conserved in the rat and mouse promoters and was shown to be capable of mediating transcriptional trans-activation in HER2/neu-overexpressing MDA-MB453 cells while having little effect in a control cell line that expresses basal levels of HER2/neu. Knowledge on interactions between this DNA element and nuclear protein factors may help us better understand the molecular mechanisms regulating HER2/neu overexpression in breast cancer cells.

Animals