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Biomedical subjects

G Zhu

Publications and source records attributed to G Zhu.

At least 127 records · Page 7Linked to original sources

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins.

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.

Adolescent↗

Pharmacokinetics and tissue disposition in monkeys of an antisense oligonucleotide inhibitor of Ha-ras encapsulated in stealth liposomes.

PURPOSE: This study examined the pharmacokinetics and tissue distribution of an antisense oligonucleotide ISIS 2503, formulated in stealth (pegylated) liposomes (encapsulated) or in phosphate-buffered saline (unencapsulated). METHODS: Encapsulated or unencapsulated ISIS 2503 was administered to rhesus monkeys by intravenous infusion. The concentrations of ISIS 2503 and metabolites in blood, plasma, and tissue samples were determined by capillary gel electrophoresis. RESULTS: Plasma concentrations of encapsulated ISIS 2503 decreased mono-exponentially after infusion with a mean half-life of 57.8 hours. In contrast, the concentration of unencapsulated ISIS 2503 in plasma decreased rapidly with a mean half-life of 1.07 hours. Both encapsulated and unencapsulated ISIS 2503 distributed widely into tissues. Encapsulated ISIS 2503 distributed primarily to the reticulo-endothelial system and there were few metabolites observed. In contrast, unencapsulated ISIS 2503 distributed rapidly to tissue with highest concentration seen in kidney and liver. Nuclease-mediated metabolism was extensive for unencapsulated oligonucleotide in plasma and tissues. CONCLUSIONS: The data suggest that stealth liposomes protect ISIS 2503 from nucleases in blood and tissues, slow tissue uptake, and slow the rate of clearance from the systemic circulation. These attributes may make these formulations attractive for delivering oligonucleotides to sites with increased vasculature permeability such as tumors or sites of inflammation.

Animals↗

B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion.

The B7 family members B7-1 and B7-2 interact with CD28 and constitute an essential T-cell co-stimulatory pathway in the initiation of antigen-specific humoral and cell-mediated immune response. Here, we describe a third member of the B7 family, called B7-H1 that does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). Ligation of B7-H1 co-stimulated T-cell responses to polyclonal stimuli and allogeneic antigens, and preferentially stimulated the production of interleukin-10. Interleukin-2, although produced in small amounts, was required for the effect of B7-H1 co-stimulation. Our studies thus define a previously unknown co-stimulatory molecule that may be involved in the negative regulation of cell-mediated immune responses.

Amino Acid Sequence↗

A major quantitative-trait locus for mole density is linked to the familial melanoma gene CDKN2A: a maximum-likelihood combined linkage and association analysis in twins and their sibs.

Important risk factors for melanoma are densely clustered melanocytic nevi (common moles) and mutations in the p16 (CDKN2A) gene. Nevi may be subclassified as raised or flat. In our sample, raised nevi were 27% of the total, and the two kinds had a correlation of.33. Correlations for total-nevus count (TNC) in 153 MZ and 199 DZ twin pairs were.94 and.60, respectively, which are compatible with a very-high degree of genetic determination. We hypothesized that some of the genetic variance might be due to variation in the p16 gene. Analysis of linkage to a highly polymorphic marker (D9S942), located close to p16, detected quantitative-trait-loci (QTL) effects accounting for 27% of variance in TNC, rising to 33% if flat but not raised moles were considered. Total heritability was higher for raised (.69) than for flat (.42) moles, but QTL linkage was 0 for raised moles, whereas it accounted for 80% of the heritability of flat moles; additionally, family environment accounted for only 15% of variance in raised versus 46% in flat moles. These findings suggest that raised and flat nevi have very different etiologies. Longer alleles at D9S942 were associated with higher flat-mole counts, and a novel modification to a within-sibship association test showed that this association is genuine and not due to population stratification, although it accounts for only 1% of total variance. Since germline mutations in the exons of CDKN2A are rare, it is likely that variants in the noncoding regions of this gene, or in another gene nearby, are responsible for this major determinant of moliness and, hence, of melanoma risk.

Child↗

Effect of osteoblastic culture conditions on the structure of poly(DL-lactic-co-glycolic acid) foam scaffolds.

Poly(DL-lactic-co-glycolic acid) (PLGA) foams are an osteoconductive support that holds promise for the development of bone tissue in vitro and implantation into orthopedic defects. Because it is desirable that foams maintain their shape and size, we examined a variety of foams cultured in vitro with osteoblastic cells. Foams were prepared with different porosities and pore sizes by the method of solvent casting/porogen leaching using 80, 85, and 90 wt% NaCl sieved with particle sizes of 150-300 and 300-500 microm and characterized by mercury intrusion porosimetry. Foams seeded with cells were found to have volumes after 7 days in static culture that decreased with increasing porosity: the least porous exhibited no change in volume while the most porous foams decreased by 39 +/- 10%. In addition, a correlation was observed between decreasing foam volume after 7 days in culture and decreasing internal surface area of the foams prior to seeding. Furthermore, foams prepared with the 300-500 microm porogen had lower porosities, greater mean wall thicknesses between adjacent pores, and larger volumes after 7 days in culture than those prepared with the smaller porogen. Two culture conditions for maintaining cells, static and agitated (in a rotary vessel), were found to have similar influences on foam size, cell density, and osteoblastic function for 7 and 14 days in culture. Finally, we examined unseeded foams in aqueous solutions of pH 3.0, 5.0, and 7.4 and found no significant decrease in foam size with degradation. This study demonstrates that adherent osteoblastic cells may collapse very porous PLGA foams prepared by solvent casting/particulate leaching: a potentially undesirable property for repair of orthopedic defects.

Alkaline Phosphatase↗

Reconstitution of a bacterial/plant polyamine biosynthesis pathway in Saccharomyces cerevisiae.

Polyamine synthesis in most organisms is initiated by the decarboxylation of ornithine to form putrescine via ornithine decarboxylase (ODC). Plants, some bacteria and some fungi and protozoa generate putrescine from arginine, via arginine decarboxylase (ADC) and agmatine ureohydrolase (AUH) or agmatine iminohydrolase. A polyamine-requiring strain of Saccharomyces cerevisiae with a mutation in the gene encoding ODC was transformed with plasmids bearing genes encoding Escherichia coli ADC and AUH. Transformants regained the ability to grow in the absence of exogenous polyamines and contained enzyme activities consistent with the presence of both prokaryotic enzymes. Similar results were obtained when a plasmid containing a gene encoding oat (Avena sativa L.) ADC was substituted for the E. coli gene. These data demonstrate the successful complementation of a yeast biosynthetic polyamine synthesis defect by genes encoding an alternative pathway found in bacteria; they also show that plant ADC can substitute for the bacterial enzyme in this pathway. The recombinant yeast provides a tool for the study of the functional properties of these enzymes and for discovery of compounds that specifically inhibit this pathway.

Avena↗

Therapeutic effect of abstinence capsule on withdrawal symptoms of heroin addicts.

435 heroin addicts were treated for 10 days to evaluate the therapeutic effectiveness of abstinence capsule on heroin withdrawal symptoms and its main adverse actions. Lofexidine was applied in a control group of 48 addicts. The single blind method and some determination methods used internationally were employed to evaluate the therapeutic effectiveness and adverse actions of the drugs. The results showed that the abstinence capsule has better therapeutic effectiveness, with less adverse actions, wider safety range, longer time of action and less cost than lofexidine.

Adolescent↗

[Clinicopathologic and immunohistochemical features of vulvar Paget diseases].

OBJECTIVE: To improve understanding the factors of development, recurrence and prognosis of vulvar Paget disease (VP). METHODS: Clinicopathologic analyses were performed in 14 patients with VP treated in our hospital from Jan 1959 to Dec 1996. Immunohistochemical stainings for CK7, 34 beta E12, carcinoembryonic antigen (CEA), C-erbB2 and HMB45 were carried out in 6 cases. RESULTS: The mean duration from manifestation of symptoms to diagnosis was 57.1 months. The local recurrent rate after operation was 69%. The mean period from the initial operation to recurrence was 68.8 months. 2 cases out of 4 intraepithelial VP cases recurred with positive surgical margins, but no recurrence in of the other 4 cases with negative surgical margins. Immunohistochemical stainings for CK7 and CEA in 6 cases with VP showed strong positive, whereas for 34 beta E12 and HMB45 in all 6 cases were negative, and for C-erbB2 in 2 cases were positive. CONCLUSIONS: The findings that CK7 and CEA positive in Paget cell of VP, whereas 34 beta E12 and HMB45 negative, suggests that Paget cell of VP possesses characteristics of adenocarcinoma. The recurrence of VP correlates with positive surgical margins. Long term follow-up after operation is essential for VP. The prognosis of intraepithelial and minimally invasive VP was favourable, adjunctive radiotherapy after operation was effective for invasive VP in our studied cases.

Adult↗

[The regulation of estrogen and tamoxifen to bcl-2 oncogene in endometrial carcinoma].

OBJECTIVE: To study the regulation mechanisms of bcl-2 oncogene in endometrial carcinoma. METHODS: A reverse transcription-polymerase chain reaction (RT-PCR) method was utilized to quantitate bcl-2 mRNA levels which regulated by estrogen(17-beta-estradiol) and tamoxifen in estrogen receptor (ER)(+) RL-952 endometrial carcinoma cells. RESULTS: bcl-2 mRNA level was detected in ER(+) RL-952 cells. 17-beta-estradiol stimulated a concentration-dependent increase in bcl-2 mRNA level, while tamoxifen lead to a concentration-dependent decrease in bcl-2 mRNA level. CONCLUSIONS: bcl-2 oncogene expression in ER(+) endometrial carcinoma is regulated by estrogen and antiestrogen. Estrogen may up-regulate the cell bcl-2 level to inhibit cell apoptosis, while tamoxifen may down-regulate the cell bcl-2 level and induce apoptosis.

Carcinoma↗

Relationship of vascular remodeling and restenosis after interventional therapy: an experimental study on rabbit atherosclerotic iliac artery model.

OBJECTIVE: To evaluate the relative contribution of every part of vascular wall to lumen area loss after angioplasty. METHODS: Angioplasty was performed on rabbits iliac atherosclerosis model. Histomorphometric results of histological cross-sectional areas from target vessels of animals killed immediately after angioplasty (acute group, n = 20) were compared with those of the same areas from animals killed 4 weeks after the procedure (chronic group, n = 23), when restenosis occurred in this model. If taking 30% diameter decrease as restenosis criteria, the chronic group was further divided into two subgroups (nonrestenosis subgroup [NRS, n = 9] and restenosis subgroup [RS, n = 14]) and their histomorphometric results were also compared. RESULTS: The lumen area decreased by 0.48 mm2 from acute group to chronic group (acute group 0.86 +/- 0.23 mm2 vs chronic group 0.38 +/- 0.20 mm2, P < 0.001). Over the same period intimal area increased by 0.12 mm2 and the area circumscribed by inner elastic lamina (IEL area) decreased by 0.36 mm2. Intimal hyperplasia could only explain 25% of the later lumen area loss. We further found a more significant IEL area decrease in RS subgroup than in NRS subgroup (0.68 +/- 0.35 mm2 vs 0.94 +/- 0.14 mm2, P < 0.05), despite the same intimal area (0.39 +/- 0.16 mm2 vs 0.41 +/- 0.31 mm2, P = NS). The different lumen area between RS subgroup and NRS subgroup (0.27 +/- 0.10 mm2 vs 0.55 +/- 0.10 mm2, P < 0.001) was predominantly due to the greater IEL shrinking in RS subgroup. CONCLUSION: Our data indicate that later lumen area loss after angioplasty results from both intimal hyperplasia and arterial shrinking (remodeling), but the latter plays a much greater role.

Angioplasty, Balloon, Coronary↗

Proliferative activity in cervical intraepithelial neoplasia and cervical carcinoma.

OBJECTIVE: To detect the proliferative activity of cervical cells in cervical intraepithelial neoplasia (CIN) and cervical carcinoma by using proliferating cell nuclear antigen (PCNA) immunohistochemistry and mitotic index (MI). METHODS: Sixty specimens of CIN and cervical carcinoma from patients treated at the Obstetrics and Gynaecology Hospital, Shanghai Medical University, were analyzed. Among them, 8 were CIN I-II, 16 CIN III, 18 squamous carcinoma, and 18 adenocarcinoma. Serial 4 microns sections were prepared for haematoxylin and eosin (HE) staining to observe mitotic figure and pathological grading and for immunohistochemical staining of PACN which was performed by murine monoclonal antibody PC 10 (DAKO-PCNA). RESULTS: PCNA index (PI) and MI of CIN III and cervical carcinoma were significantly higher than those of normal cervix and CIN I-II. PI and MI increased with progress of disease. In addition, higher level of PI was correlated with higher level of MI, and higher levels of PI and MI were related with higher histological grade. However, there was no significant relationship between PI, MI, clinical staging, and lymph node metastases. CONCLUSION: PCNA and mitotic figure are useful for evaluating proliferative activity in CIN and cervical carcinoma, and could be used to distinguish CIN III from CIN I-II and evaluate the malignant potential of tumour tissues.

Adenocarcinoma↗

[Vascular endothelial growth factor gene therapy for peripheral artery disease: experimental study].

OBJECTIVE: To Study experimentally VEGF gene for treatment of peripheral artery disease. METHODS: The human VEGF cDNA was cloned into the eukaryotic expression vector pcD2. Using gene suture, the recombinant plasmid was transferred into the hindlimbs' adductor of Rhesus monkey, of which the distal end of the external iliac arteries were ligated and the femoral arteries were completely excised. With angiography, the biological effect of VEGF gene in experimental animals was investigated. Safety tests were analyzed by transferring of VEGF into mouse, rat, and Rhesus monkey, evaluated by biochemistry analysis, histopathological examination, PCR, and indirect ELISA. RESULTS: The transfer of VEGF gene stimulated the formation of focal microvessels, established collateral circulation, and augmented blood perfusion. The system had no adverse effect and remarkable pathological change in mouse, rat, and Rhesus monkey. CONCLUSION: The experimental studies indicated that VEGF would be effective and safe for clinical trial after approval.

Animals↗

[Effect of tripterine on concentration of free calcium and hydrogen in vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of tripterine on concentration of free calcium (Ca2+) and hydrogen (H+) in vascular smooth muscle cells (VSMC). METHODS: By using fluorescence staining method, changes of the free calcium and hydrogen in single VSMC were studied with laser confocal scanning analyzer after different concentrations of fetal calf serum (FCS), tripterine and FCS plus tripterine were added into the culture pools respectively. RESULTS: The concentration of intracellular Ca2+ increased rapidly, sequentially and significantly after addition of 30% FCS (P < 0.05), 0.3 mg/L tripterine plus 30% FCS had inhibition effect on the concentration of the intracellular Ca2+, 20% FCS reduced the concentration of intracellular H+ significantly (P < 0.05), and 0.2 mg/L tripterine caused a significant increasing concentration of H+ (P < 0.05). CONCLUSION: Tripterine has an antagonistic action on the increasing concentration of intracellular Ca2+ induced by FCS, the inhibitory effect of tripterine on the Ca2+ channel of VSMC membrane may be responsible for this new mechanism.

Animals↗

[The features of coronary angiography in coronary heart disease with non-insulin-dependent diabetes mellitus].

OBJECTIVE: To study the clinical and angiographical characteristics of coronary heart disease (CHD) in CHD patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS: The study was carried out by case control analysis of the clinical manifestations and the data from cine selective coronary angiography. RESULTS: CHD patients with NIDDM tended to have multiple cardiovascular risk factors. It is likely that NIDDM contributed more to dyslipidemia in the female than in the male. Unstable angina pectoris was found more frequently in CHD patients with NIDDM than in those without. The female CHD patients with NIDDM were more frequently afflicted with myocardial infarction. Moreover, CHD patients with NIDDM had much greater extent of coronary vessel involvement and more diffuse vascular lesion. CONCLUSION: The clinical and angiographical findings are quite different in CHD patients with and without NIDDM. The lesions in the coronary arteries tend to be more severe and diffuse in patients with NIDDM.

Adult↗

[Analysis of 16 cases with aggressive fungal maxillary sinusitis].

OBJECTIVE: To improve the diagnosis and treatment level of aggressive fungal maxillary sinusitis. METHOD: 16 cases were diagnosed with CT. Caldwell-Luc's surgery was done in 13 cases and Lima surgery in 3 cases. None of them were treated by antifungal agents. RESULT: It showed osteolytic damage with bony defect which was different from expanded bony defect caused by benign tumor, but similar to malignant tumor. No recurrence occurred as followed from 6 months to 2 years. CONCLUSION: Computed tomography is very important in its diagnosis. Early explorative operation is useful in making definite diagnosis.

Adult↗

[Analysis of HPLC of isomers of nitrotoluene and nitrobenzoic acid].

Nitrotoluene and nitrobenzoic acid isomers were separated completely in less than 10 minutes by Kromasil C18 (200 mm x 4.6 mm i.d.), when V(CH3OH):V(H2O):V(THF) = 55:44:1 with beta-CD of 0.02 mol/L at flow rate of 2.0 mL/min (former 4 min) and 2.6 mL/min (later 6 min). Detector of UV-254 at 0.04 AUFS was used.

Chromatography, High Pressure Liquid↗

[Effect of 17 beta-estradiol on activity and gene expression of fibrinolytic factor in human umbilical vein endothelial cell].

OBJECTIVE: To study the effect of 17 beta-estrodial on fibrinolytic factor in human umbilical vein endothelical cell (HUVEC). METHODS: When different concentration of 17 beta-estrodial including 10(-10) mol/L (the group E1), 10(-8) mol/L (the group E2), 10(-6) mol/L (the group E3) were treated in original cultured HUVEC, the changes of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) were measured by spectrophotometric assay, and the level of message RNA were examined by in situ hybridization. The changes of intracellular free calcium concentration([Ca2+]i) in single cells were observed by kinetic observation with Laster Confocal Microscope. RESULTS: The t-PA activity both in E1 and E2 were higher than control (P < 0.05 respectively). The t-PA expression in E1, E2, and E3 were increased. The concentration of intracellular free calcium had an elevated and declined curve under the supraphysiological doses of estrodial and declined in incubation with 17 beta-eatrodial at 10(-6) mol/L. CONCLUSIONS: These suggeste that the protection of 17 beta-estrodial on cardivascular system is associated with high fibrinolytic activity and t-PA expression as well as with the change of [Ca2+]i.

Calcium↗