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Biomedical subjects

D Li

Publications and source records attributed to D Li.

At least 433 records · Page 24Linked to original sources

Coronary MR angiography.

Coronary MR angiography has developed rapidly over the past several years. Not only is research being performed at academic centers but industry is also investing in dedicated contrast agents and cardiac MR imaging platforms. Although current coronary MR angiography has limited clinical utility, its place within the assessment of ischemic cardiac disease is evolving. The technology currently under investigation holds much promise, especially when one considers that MR has the potential to provide information currently supplied by the performance of a number of screening tests. It would be far more cost-effective to perform a single MR examination than to perform a stress echo, rest-stress nuclear medicine examination and a conventional coronary angiogram. In addition, clinicians need information about coronary flow and myocardial perfusion. Although some of this information can be currently obtained with an intravascular Doppler flow wire or by positron emission tomography, MR angiography offers the advantages of being both noninvasive and more easily accessible in comparison to either method. The combined information promised by a comprehensive cardiac MR examination that includes coronary MR angiography as a component is an exciting prospect.

Contrast Media↗

Combination surgery and nonviral interleukin 2 gene therapy for head and neck cancer.

We have developed a novel nonviral interleukin 2 (IL-2) gene therapy that demonstrates significant treatment-specific, antitumor efficacy in combination with subtotal surgical resection in a head and neck cancer murine model. Treatment of established head and neck tumors in immunocompetent mice was performed via direct injection with a cationic liposome composed of DOTMA and cholesterol formulation carrying DNA plasmid for human IL-2 (hIL-2) gene expression. ELISA assays of tumor extracts 24 h after treatment of hIL-2 gene therapy revealed increased local hIL-2 production as well as a formulation-specific secondary induction of murine IFN-gamma and IL-12. We hypothesize that the paracrine production of multiple cytokines after IL-2 single gene transfer is important for generating a therapeutic effect, and that this strategy will be well tolerated and effective in combination with surgery for head and neck cancer. In animal experiments where surgery was performed in conjunction with an operative site injection of hIL-2 plasmid formulation, no pre-, intra-, or postoperative toxicity or compromise to wound healing was identified. In murine experiments combining partial surgical resection with the nonviral gene therapy, significant antitumor efficacy was demonstrated in the hIL-2 plasmid formulation group compared with empty plasmid formulation and lactose-injected controls. In a separate experiment using smaller tumor sizes, we also demonstrated that treatment outcomes were dependent on the technical aspect of the actual treatment injection as well as visualization with surgical access. The hIL-2 plasmid formulation gene therapy induces local expression of multiple cytokines, results in treatment-specific antitumor effects, and circumvents many of the concerns and toxicity encountered with viral gene transfer. These data support the need for continued preclinical investigation and the consideration of human clinical trials for combination nonviral hIL-2 gene therapy and surgery for head and neck cancer.

Animals↗

Lipoprotein(a), essential fatty acid status and lipoprotein lipids in female Australian vegetarians.

In the present study we investigated serum lipoprotein(a) [Lp(a)] levels, plasma lipids, the serum phospholipid polyunsaturated fatty acid profile and correlates of serum Lp(a) in healthy free-living female vegetarians (n=50) and omnivores (n=24) to assess differences which may have implications for cardiovascular risk. Dietary saturated fat and total plasma cholesterol were significantly lower in the vegetarians compared with omnivores. The mean serum Lp(a) concentration was lower in the vegetarians (171 mg/l) than in the omnivores (247 mg/l). The serum Lp(a) concentration was significantly negatively correlated with carbohydrate intake (as % of energy), and positively correlated with plasma total cholesterol. Compared with the omnivores, the vegetarians had significantly lower concentrations of 20:3,n-6, 20:4,n-6, 22:5,n-6, 20:5,n-3, 22:6,n-3 and total n-6 and n-3 polyunsaturated fatty acids, and a lower n-3/n-6 polyunsaturated fatty acid ratio, in serum phospholipids. Lower concentrations of plasma total cholesterol, serum phospholipid total fatty acids, total saturated fatty acids and arachidonic acid, and a tendency towards a lower serum Lp(a) concentration, in vegetarians may have beneficial effects on cardiovascular disease risk. However, the decreased concentration of serum phospholipid n-3 polyunsaturated fatty acids may potentially promote thrombotic risk. Based on the present data, it would seem appropriate for omnivores to reduce their dietary intake of total fat and saturated fat in order to decrease their plasma cholesterol, and vegetarians should perhaps increase their dietary intake of n-3 polyunsaturated fatty acids, and thus improve the balance of n-3/n-6, in order to reduce any thrombotic tendency that might increase their generally low risk of cardiovascular disease.

Adult↗

Changes in levels of normal ML-1 gene transcripts associated with the conversion of human nontumorigenic to tumorigenic phenotypes.

Evaluation of malignant human tumors in a xenobiotic nude mouse system has demonstrated that not all cells in tumors exhibit the capacity to form progressively growing tumors. However, nontumorigenic cells isolated from human tumors can be converted to a tumorigenic phenotype in nude mice by treatment with chemical carcinogens or by transfection with antisense to tumor suppressor genes. A newly discovered gene, designated ML-1, appears to be associated with tumorigenesis, because an ML-1 antisense cDNA construct, transfected into nontumorigenic, anchorage-independent growth (AIG) cells, was sufficient to convert these cells into a tumorigenic phenotype. The AIG cells transfected with ML-1 antisense cDNA constructs and converted to tumorigenic cells did not exhibit expression of normal ML-1 mRNA transcripts in the converted cells when evaluated by Northern analysis, whereas premalignant and normal cells expressed ML-1 transcripts at a high level. The converted cells exhibited a loss of growth control and produced tumors in a surrogate nude mouse that were greater than 2.0 cm in less than 2 months. The ML-1 gene has a DNA sequence that is 2177 bp in size and is located on chromosome number 13 on the q arm at site 12-14. Sequence analysis and investigation of GenBank sequences indicate that this is a newly described human gene.

Amino Acid Sequence↗

[Gene analysis of acute sporadic HEV in the southern areas of China].

OBJECTIVE: To investigate the existing different gene sequences of hepatitis E virus (HEV) in the southern areas of China. METHODS: Eight acute-phase sera of sporadic patients with hepatitis E in Xiamen were tested by reverse transcription--polymerase chain reaction(RT-PCR). Two cases of them were positive. The fifth passage culture of Guangzhou G93-2 strain of HEV was also detected by RT-PCR. The positive RT-PCR products underwent cloning and nucleotide sequencing. RESULTS: The homology of nucleotide and the amino acid between Xiamen X-S1 and Guangzhou G93-2 strain are 99.2% and 97.5%. The homology of nucleotide and the amino acid sequences of Xiamen strain and Guangzhou strain are 79.9% and 86.3% compared with the Burmese strain (Bur-121) and our country Xinjiang strain (87A), and are 77.4% and 86.3% against Mexican strain. CONCLUSION: The results suggest that there is a different genotype of HEV in the southern areas of China.

Acute Disease↗

32P-postlabelling with high-performance liquid chromatography for analysis of abundant DNA adducts in human tissues.

Abundant complex DNA adducts can be detected in human tissues by a combined 32P-postlabelling and high-performance liquid chromatography (HPLC) method. The HPLC profiles reveal a panorama of nuclease P1-resistant human adducts, which are not among the known human DNA adducts and are suspected of being endogenous. Lipid peroxidation-induced DNA adducts and I-compounds are two possible candidates for these adducts. Therefore, we performed two experiments: one was to identify chromatographically the lipid peroxidation-induced adducts among other human adducts with two acrolein- and crotonaldehyde-derived propano adduct standards (Acr-dG3 and Cro-dG1&2) and a structurally unknown adduct (Cro-DNA) derived from crotonaldehyde-treated DNA; and the other was to analyse the adducts in breast tissue from patients with breast cancer and from controls and to compare their behaviour with that of I-compounds in cancerous tissues. In the first experiment, Acr-dG3 and Cro-dG1 were detected in three human lung tissues, at levels ranging from 3.4 to 8.9 (x 10(-8)) and from not detectable to 2.9 (x 10(-8)), respectively. Acr-dG3 and Cro-DNA were detected in three human colon tissues, at levels of 0.2-0.4 (x 10(-8)) and 1.2-3.4 (x 10(-8)), respectively. In the second experiment, adjacent and tumorous breast tissues from 15 patients with breast cancer (of an average age of 33.4 years) and normal breast tissue from 18 controls (of an average age of 57.3) were analysed for the abundant complex adducts. The total adduct levels in the adjacent and tumorous tissues were lower than in the normal tissues (with medians of 8.0, 11.8 and 13.3 (x 10(-7)), respectively). Significant differences in the adduct levels between adjacent or tumorous tissues and normal tissues were observed in three HPLC peaks, and age was significantly associated with three peaks. These results are consistent with our speculation that the abundant adducts are comprised of lipid peroxidation-induced adducts and human homologues of I-compounds.

Acrolein↗

Variability of adenovirus receptor density influences gene transfer efficiency and therapeutic response in head and neck cancer.

Despite encouraging preclinical studies in many tumor types including head and neck squamous cell carcinoma (HNSCC), initial clinical trials with adenovirus-mediated gene therapy have been disappointing. Although the adenovirus is a "highly efficient vector," it is still limited by the extent of effective in vivo transduction. In our studies with multiple human HNSCC cell lines, we have noted a variation in both in vitro and in vivo responses to the same recombinant adenovirus therapeutic construct. We hypothesize that adenovirus receptor density among tumor cell populations, even of the same histology, greatly influences transduction efficiency and therapeutic results of a variety of adenovirus-based gene therapy strategies. To investigate this hypothesis, the numbers of adenovirus receptors on three well-characterized HNSCC cell lines were determined. Marker and cytokine gene transfer efficiencies as well as therapeutic outcomes after adenovirus-mediated tumor suppressor gene and suicide gene therapies were evaluated and correlated with receptor status. A 5-fold variation in adenovirus receptor density was identified among the HNSCC cell lines (P < 0.002, t test). This variation directly correlated with adenovirus type 5 (Ad5)-mediated green fluorescent protein marker gene and Ad5-interleukin 2 cytokine gene transfer efficiency and resulting protein expression in each individual cell line. The receptor density also directly correlated with therapeutic response after Ad5-thymidine kinase or Ad5-p16 gene transfer in each HNSCC line. The role of the adenovirus receptor in gene transfer efficiency was further supported by recombinant Ad5 fiber knob blocking experiments. The marker gene transfer was increasingly blocked by the same concentration of Ad5 recombinant fiber knob in relation to decreasing levels of adenovirus receptor in the HNSCC lines. An Ad5 recombinant construct that carries the shared coxsackie and adenovirus receptor (CAR) was created and used to up-regulate receptors on each cell line. Ad5-CAR infection significantly increased Ad5-beta-Gal gene transfer efficiency and expression (P = 0.0003, Mann-Whitney test). This increased marker gene expression remained consistent with the established pattern of gene transfer efficiency among the HNSCC cell lines. These data confirm the importance of the adenovirus receptor on individual tumor cell lines with respect to investigating novel adenovirus-mediated gene therapy strategies. This work further supports consideration of assaying adenovirus receptor status, even in tumors of the same histology from patients enrolled in gene therapy clinical trials. Adenovirus receptor status may prove valuable for selecting or stratifying patients as well as assessing outcomes among patients within adenovirus-based cancer gene therapy trials.

Adenoviruses, Human↗

New experimental model to study the bone interface of endosseous implants: an in vitro three-dimensional model of cell culture.

To set up a three-dimensional culture model of endosseous implant material-osteoblast, titanium (Ti) discs were placed onto confluent cellular layers of human fetal osteoblasts that were cultured in calcifying conditions. Follow-up observations of living cells with phase-contrast microscopy and histological observations of the cell-Ti disc interface with ordinary microscopy and transmission electron microscopy were used to monitor and verify the formation of three-dimensional cellular structures at the osteoblast-Ti disc interface. These methods were further used to study osteoblast cell behavior during the early stage of bone healing in this three-dimensional cellular model. The follow-up observation showed that, upon the placement of the Ti disc, cells migrated from the cellular layer and attached to the rim of the disc, forming cell bridges. Cells continued to attach and orient throughout the culture time. A cellular multilayer at the osteoblast-Ti interface was formed, which resulted in the three-dimensional model. Furthermore, transmission electron microscopy observation showed that there was a mineralizing process at the osteoblast-Ti disc interface just like bone, which confirms the reality of this model. Histological observations with conventional microscopy demonstrated the interfacial relation between biomaterial and cells. If osteoblasts were replaced by other types of cells, this model could be used to study the other kinds of interfaces.

Cell Adhesion↗

Pharmacokinetics of 2-hydroxyflutamide, a major metabolite of flutamide, in normal and CCl4-poisoned rats.

AIM: To study the pharmacokinetics of 2-hydroxyflutamide (HF), a major active metabolite of flutamide (Flu), in normal and CCl4-poisoned rats. METHODS: Normal and CCl4-poisoned rats were given i.g. HF 25 mg.kg-1. HF concentrations of plasma were determined by HPLC with YWG C 18 column, Flu was used as an internal standard. The mobile phase was composed of methanol: water = 3:2 (vol), and absorbance was measured at lambda 295 nm. RESULTS: HF elimination was inhibited in CCl4-poisoned rats compared with normal rats. K decreased from (0.11 +/- 0.05) to (0.05 +/- 0.01) h-1 (P < 0.01), T1/2 was prolonged from (6.8 +/- 1.9) to (14 +/- 4) h (P < 0.01), Cl decreased from (0.18 +/- 0.06) to (0.12 +/- 0.02) L.kg-1.h-1 (P < 0.05), AUC increased from (149 +/- 47) to (226 +/- 54) mg.L-1.h (P < 0.05). CONCLUSION: This HPLC assay was sensitive and precise, and the elimination of HF was inhibited due to CCl4 poisoning.

Androgen Antagonists↗

Flutamide suppressed prostate hypertrophy in rats and mice.

AIM: To study the suppressive effect of flutamide (Flu) on benign prostate hypertrophy. METHODS: The effect of Flu 10, 25, and 50 mg.kg-1 i.g. on the prostate was tested in orchiectomized rats with s.c. testosterone daily for 30 d and in mice implanted with homologous strain fetal mouse urogenital sinus for 14 d. RESULTS: 1) Flu dose-dependently suppressed the weight and volume of each lobe of the prostate to about 10%-50% of control. Also, the acini and height of epithelial cells atrophied. The effect was more powerful than that of estradiol (Est). 2) The weight and volume of the mouse prostate diminished in Flu-treated groups, but the dose-response relationship was seen only in volume. In this model, Est was better than Flu. CONCLUSION: Flu possesses the suppressive action on benign prostate hypertrophy.

Androgen Antagonists↗

Metastatic conversion of chemically transformed human cells.

A linear model for human cell metastasis has been developed in vitro from chemically transformed normal human cells. The chemically transformed cells are nontumorigenic in nude mice, but can be converted to a tumorigenic phenotype by transfection with a nondirectional cDNA library or antisense cDNA to the ML-1 gene. The primary transfected cell line (TR1T) forms localized, progressively growing tumors in nude mice that do not invade into the surrounding tissue. This tumorigenic TR1T cell line could be advanced into a metastatic stage following an additional transfection (TR2M cell line) with the cDNA expression library or antisense cDNA to the ML-1 gene. Metastatic cells, selected from tumors that were attached to internal organs, exhibited an increase in invasiveness as measured in vitro using an invasion chamber. The metastatic cells also exhibited an increased expression of matrix metalloproteinase-1 (MMP-1), although MMP-1 was not part of the cDNA that was transfected into either the TR1T cells or the doubly transfected metastatic TR2M cells. These data suggest that the increase in MMP-1 expression was a secondary downstream event responding to an upstream genetic change that initiated the conversion of cells from a tumorigenic to a metastatic stage. In summary, human cell lines representing premalignant, malignant, and metastatic phenotypes have been established in culture that can be used to identify gene changes that occur as normal human cells progress to a metastatic stage during tumor development. One gene, ML-1, that is found in the expression library appears to be involved in malignant progression, because ML-1 antisense cDNA will convert chemically transformed cells to both tumorigenic and metastatic stages, and cells from both local and metastatic tumors have a reduced or complete loss of expression of the ML-1 gene.

Animals↗

[Study of histopathology of endometrium following termination of early pregnancy using mifepristone].

OBJECTIVE: To explore the causes of abnormal uterine bleeding following termination of early pregnancy using mifepristone. METHODS: 19 specimens were obtained by curettage on the day immediately after expulsion of gestational sac, 40 specimens on the 7th postabortal day and 20 specimens during 2-12 weeks after induced abortion using mifepristone respectively. The histopathologic changes of the specimens were observed by HE staining, and the expression of human choronic gonadotropin (hCG) and human placental lactogen (hPL) by immunohistochemical studies as well as phloxine-tartrazine staining and Gordon Sweets staining. RESULTS: It showed that decidua shedding retarded, especially basal decidua. Immunohistochemical studies demonstrated the trophoblasts were still active and might affect pathological changes of local endometrium. The specific granules of endometrial granulocytes disappeared, together with disintegration of the reticular fibers. But in the group which curettage was indicated for abnormal bleeding 2 weeks after abortion, the main cause was incomplete abortion. CONCLUSIONS: In addition to incomplete abortion, the retardation of decidua shedding and the impairment of endometrium regeneration were responsible for the abnormal uterine bleeding following termination of early pregnancy using mifepristone. The incomplete dissolution of the reticular fibers in basal decidua may induce decidua shedding retardation and incomplete abortion.

Abortifacient Agents, Nonsteroidal↗

[Classification and surgical correction of hump nose].

OBJECTIVE: To establish a new classification of hump nose and to develop operative techniques based on its characteristics in Chinese patients. METHODS: This paper presents and summarises 68 cases of hump nose. According to the anatomic structure of the hump nose, we classify it into four types: small hump type I and II, moderate hump and large hump. Based on the classification of hump nose, two operative methods were developed-osteotomy and non-osteotomy. RESULTS: From 1990 to 1997, 68 cases of hump nose were operated on. Postoperative follow-up for 1-18 months showed satisfactory results. CONCLUSION: By means of this classification and the operative techniques, good result can be obtained for the correction of the majority of hump noses in the Chinese.

Adult↗

Factors involved in the neuronal death during postischemic reperfusion: experimental study in rabbits.

OBJECTIVE: To explore the main pathogenic factors in the development of neuronal death during normothermic reperfusion in rabbits. METHODS: Ninety-six New Zealand rabbits were randomly allocated into two groups: group I served as non-ischemic controls; group II served as postischemic normothermic reperfusion models. Complete cerebral ischemia was induced by the four-vessel model for 30 minutes. After ischemia, rabbits in group II were further divided into three subgroups according to the duration of reperfusion: subgroup A, 30 minutes; subgroup B, 180 minutes and subgroup C, 360 minutes. Twenty-eight biochemical parameters in the brain were measured, and neuronal changes were observed by histomorphological assessment. Neurons of 12 regions were differentiated into four types: type A (normal), type B (mildly damaged), type C (severely damaged) and type D (necrotic). Bivariate correlate analysis between the levels of biochemical parameters and the percentages of each type of neurons was carried out. RESULTS: The main parameters involved in the progressive decrement of type A neurons were VIP, beta-EP, PGI2, T3, T4 and Na+, K(+)-ATPase; in the increment of type B were beta-EP and TXB2; in the increment of type C were GLU and TXB2/PGI2 respectively; in the stepwise increment of percentages of type D neurons were T4, Na+, K(+)-ATPase, GLU, T3 and VIP (P < 0.05). CONCLUSION: The main factors involved in the development of neuronal death during postischemic normothermic reperfusion in rabbits include hypermetabolism, deactivation of Na+, K(+)-ATPase, release of excitatory amino acids and disorder of neuropeptides.

Animals↗

[Serum levels of soluble intercellular adhesion molecule 1 in malignant lymphoproliferative disorders].

OBJECTIVE: To investigate the correlation of serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) with clinical situation and treatment outcome in lymphoproliferative disorders. METHODS: Serum sICAM-1 levels were measured by immunoenzymatic assay. RESULTS: Pre-treatment serum sICAM-1 levels were above normal in 41% (9/22) of multiple myeloma (MM), 53% (17/32) of non-Hodgkin's lymphoma (NHL) and 63% (12/19) of acute lymphocytic leukemia (ALL) patients. Serum sICAM-1 levels in MM were positively correlated with Bataille stages, but were not related to Durie stage. Meanwhile, sICAM-1 levels in NHL were associated with the category of pathology, Ann Arbor stage and B symptom, but were not related to serum LDH levels. sICAM-1 levels were significantly higher in ALL patients complicated with central nervous system leukemia (CNSL) than in those without CNSL. Patients with elevated serum sICAM-1 levels had poorer treatment outcomes. Serum sICAM-1 levels were returned to normal at remission. CONCLUSION: Measurement of serum sICAM-1 levels in lymphoproliferative disorders patients is helpful for judging the clinical status and treatment outcome.

Adult↗

In vitro activities of five antifungal agents against pathogenic Exophiala species.

OBJECTIVES: To examine the in vitro activities of five antifungal agents against common pathogenic Exophiala species; to detect the minimum inhibitory concentration (MIC) discrepancies among different drugs and different species; to evaluate the role of the influence factors in MIC determination; and to establish a standard method for the antifungal susceptibility testing of Exophiala spp. METHODS: MICs of itraconazole (ICZ), fluconazole, ketoconazole, amphotericin B (AmB) and 5-flucytosine against 5 species (57 strains) of Exophiala spp were determined by modified NCCLS M27-A broth microdilution method. Two inoculum sizes (0.5 x 10(3)-2.5 x 10(3) CFU/ml and 0.5 x 10(4)-2.5 x 10(4) CFU/ml) and three incubation times (4, 7 and 10 days) were evaluated. The minimum fungicidal concentrations (MFC) of itraconazole against 20 Exophiala strains were also detected. RESULTS: All the tested Exophiala species were sensitive to AmB and ICZ. MICs varied among different species and drugs. Resistant strains to different drugs existed in this genus. The proper inoculum density was about 0.5 x 10(3) CFU/ml to 2.5 x 10(3) CFU/ml, and the 4-day incubation time was suitable for more than 90% of the strains. CONCLUSIONS: AmB or ICZ may serve as the first choice in treatment of phaeohyphomycosis. A standard microdilution procedure for MIC detection of Exophiala species is established in this experiment. The inoculum size and incubation time are the essential factors in the standardization of antifungal susceptibility testing of filamentous fungi. We hope this experiment may correlate well with the clinical treatment of phaeohyphomycosis caused by Exophiala species.

Amphotericin B↗