Biomedical subjects

F Gao

Publications and source records attributed to F Gao.

At least 91 records · Page 5Linked to original sources

PubMed2001

Expression of matrix metalloproteinase-2, tissue inhibitors of metalloproteinase-1, -3 at the implantation site of rhesus monkey during the early stage of pregnancy.

We have examined the expression of MMP-2, TIMP-1, and TIMP-3 mRNA at the implantation site of rhesus monkeys during early stage of pregnancy using in situ hybridization and Northern blot analysis. The results indicate that MMP-2 mRNA was mainly localized in the chorinoic villi and epithelial plaque, suggesting that MMP-2 may be involved in the process of epithelial plaque and trophoblast invasion. TIMP-3 was specifically expressed in the cells around the spiral arteries and maternal-fetal interface. Therefore, TIMP-3 may be the main inhibitor that restricts the trophoblast invasion. The TIMP-1 mRNA was detected in trophoblast villi and maternal decidua; however, its distribution was not cell-specific, suggesting a general role in the protection of trophoblast villi and maternal decidua from proteolysis by the MMPs secreted by themselves.

Animals↗

PubMed2001

Oxidative inactivation of nitric oxide and endothelial dysfunction in stroke-prone spontaneous hypertensive rats.

This study tested the hypothesis that increased nitric oxide (NO) inactivation and concurrent peroxynitrite formation is responsible for endothelial dysfunction in the spontaneously hypertensive stroke-prone rat (SHRSP). In SHRSP, the aortic vasorelaxation to acetylcholine (ACh) was decreased (p < 0.05), but NO production was unchanged. Nitrotyrosine staining, a footprint of peroxynitrite (ONOO(-)) formation, was detected. Exposure of SHRSP to a high-salt, high-fat diet (SFD) further exacerbated hypertension and accelerated end-organ disease. A severe endothelial dysfunction [maximal ACh relaxation: 49.8 +/- 2.1 versus 94.5 +/- 1.8% in Wistar-Kyoto rats (WKY), p < 0.01], increased basal NO production (482 +/- 17 versus 356 +/- 21 nM, p < 0.01), decreased ACh-stimulated NO production (57 +/- 6 versus 112 +/- 6 nM, p < 0.01), extensive inducible NO synthase and nitrotyrosine staining, elevated nitrotyrosine content (21-fold increase over WKY), and a high percentage of cells with DNA damage were observed in the aortic tissues from these animals. Treatment of SHRSP on SFD with carvedilol restored ACh-induced vasorelaxation and NO production, inhibited nitrotyrosine formation, reduced vascular cell DNA damage, and reduced end-organ injury. These data demonstrate that endothelial dysfunction was caused by increased NO inactivation alone (SHRSP) or in combination with decreased NO production from endothelial NO synthase (SHRSP on SFD). Antioxidant treatment with carvedilol exerted significant vascular protective effects, attenuated end-organ damage, and decreased mortality under these conditions.

Acetylcholine↗

PubMed2001

Mifepristone regulates expression of apoptosis related genes Fas and FasL in mouse endometrium.

AIM: To investigate the anti-implantation mechanism of mifepriston. METHODS: In situ hybridization and immunohistochemistry were applied to determine mRNA and protein. RESULTS: After mifepriston injection, the number of implantation sites were obviously reduced, mifepriston could inhibit the embryo implantation in mouse. The expression of apoptosis related genes, Fas and FasL, in mouse endometrium was also decreased after mifepriston treatment. CONCLUSION: The expression of apoptosis related genes Fas and FasL is regulated by mifepriston and the inhibitory effect of mifepriston on the embryo implantation may be mediated by action on the Fas/FasL system.

Abortifacient Agents, Steroidal↗

PubMed2001

Role of Fas/FasL genes in azoospermia or oligozoospermia induced by testosterone undecanoate in rhesus monkey.

AIM: To investigate role of apoptosis related genes Fas/FasL in azoospermia or oligozoospermia induced by testosterone undecanoate. METHODS: TUNEL was used to detect the apoptotic signal of testicular cells. Immunohistochemistry and Western blot were used to quantitatively or qualitatively analyze the expression of these apoptosis-related proteins. RESULTS: After injection of testosterone undecanoate, both the apoptotic signal in germ cells and the expression of Fas/FasL in testis increased correlatively in a time-dependent manner, reaching a maximum level on day 30. CONCLUSION: Fas system may initiate and regulate the germ cell apoptosis induced by testosterone undecanoate.

Animals↗

PubMed2001

[Counter-effect of intermittent +Gz exposures on vasoreactivity in decline in hind body arteries of rats under simulated weightlessness].

Objective. To investigate the counter-effect of intermittent artificial gravity, the present study examined vasoreactivity changes of femoral and mesenteric arteries in rats subjected to simulated weightlessness plus standing or centrifugation. Method. Forty male Sprague-Dawley rats were divided into simultaneous control (CON), simulated weightlessness (SUS), simulated weightlessness plus 1 h standing (STD1), simulated weightlessness plus 1.5 G centrifugation (1.5 G), and simulated weightlessness plus 2.6 G centrifugation (2.6 G) groups. Responses of arteries to vasoconstrictor were examined in vitro using isolated femoral and mesenteric arterial rings. Result. The contractile responsiveness to KCl or PE of femoral and mesenteric arterial rings isolated from SUS significantly decreased as compared with CON. And those of STD1 and the two centrifuged groups significantly enhanced as compared with that of SUS. Whereas there was no difference among STD1, 1.5 G, 2.6 G and CON. Conclusion. Simulated weightlessness may result in decreased contractile responses to KCl and PE of rat femoral and mesenteric arteries. Both STD1, 1.5 G, and 2.6 G prevented the decrease of contractile response to KCl and PE of femoral arteries.

Animals↗

PubMed2001

[Current status and distribution of deafness in the elderly in several cities in China].

OBJECTIVE: To survey the current status and distribution of deafness and its effect on daily life activities in the old population. METHODS: Eight thousand two hundred and fifty-two elderly aged 60 years and above in the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and Shenyang were investigated, using a clustered random sampling methods. RESULTS: Overall crude prevalence of deafness in the elderly was found to be 33.7%, but the self-reported crude prevalence was low, only 47.1% when shown by medical examination. Crude prevalence rates were increasing with ageing, with 21.6%, 30.0%, 35.6%, 42.6%, 55.5% and 61.6% respectively (P < 0.01) in the age groups of 60-, 65-, 70-, 75-, 80-, 85- years old. Rate of deafness was highest in Beijing (58.5%), among the in-house workers (48.9%) and the lowest in scientists, teacher and health workers (28.5%). Logistic regression analysis showed that the crude prevalence was related to ageing, profession and area (P respective < 0.01). CONCLUSION: The prevalence of deafness was high in the elderly which increased with ageing with different areas, professions and the level of education. It was lower when self-reported than shown by medical examination. Prevention and treatment of deafness in the elderly should be strengthened.

Age Factors↗

PubMed2001

[Apoptosis during placentation].

Apoptosis is a normal physiological phenomenon. During the process of implantation, there are a large number of cells at the implantation site undergoing apoptosis, which has been suggested to play an important role in the regulation of endometrium decidulization and trophoblast invasion. Apoptosis mediated by Fas/FasL system may also be associated with maternal immunotolerance to the fetus. In this review, the common pathway of apoptosis and the regulation in the placenta are described.

Apoptosis↗

PubMed2001

The pathogenesis of experimental model of mitochondrial myopathy induced by germanium dioxide.

OBJECTIVE: The purpose of the study was to build up an animal model of mitochondrial myopathy in order to analyse the pathogenesis of the disease. METHODS: The skeletal muscles from Wistar rats treated with germanium dioxide for 24 weeks were analysed by histopathologic and electron-microscopic studies. A quantitative analysis was carried out in mitochondrial DNAs of these samples. The biological function of the model was determined. RESULTS: An animal model of mitochondrial myopathy was built up, in which oxygen free radicals were increased and mitochondrial DNA copies were decreased contrasted with controls. CONCLUSION: It suggested that environmental toxin may play a role in the pathogenesis of mitochondrial myopathy. The increase of oxygen free radicals is an important link causing the disease.

Animals↗

PubMed2001

A comparison of the anabolic effects of rat and bovine parathyroid hormone (1-34) in ovariectomized rats.

The current study was designed to compare the skeletal effects of comparable doses of rat parathyroid hormone 1-34 (rPTH) and bovine parathyroid hormone 1-34 (bPTH) in ovariectomized (OVX) rats. Female Sprague-Dawley rats were OVX or sham-operated at 6 months of age and maintained untreated for 28 days after surgery. Baseline control and OVX rats were sacrificed at the beginning of treatment. Beginning 28 days post-OVX, the remaining rats were subcutaneously injected daily with rPTH or bPTH at 0, 5, 25, or 50 microg/kg/d for 28 days. Bone area, bone mineral content (BMC), and bone mineral density (BMD) of the distal femoral metaphyses were determined ex vivo using dual energy X-ray absorptiometry. Quantitative bone histomorphometry was performed on undecalcified longitudinal sections of the proximal tibia from each rat. Baseline OVX rats exhibited osteopenia as demonstrated by their significantly reduced femoral BMD and proximal tibia cancellous bone volume compared with those of baseline sham controls. Both rPTH and bPTH restored bone in OVX rats by markedly stimulating bone formation in a dose-dependent manner. However, a difference in potency between the two forms of PTH was evident. The percentage increases of BMC, BMD, cancellous bone volume, trabecular thickness, mineralizing surface, and bone formation rate in the OVX rats treated with bPTH at 5 microg/kg/d were the same as or above those treated with rPTH at the 25 microg/kg/d dose level. A relative potency analysis showed that bPTH was approximately 4- to 6-fold relatively more potent than rPTH in increasing distal femoral BMD as well as cancellous bone volume, mineralizing surface, and bone formation rate of proximal tibial metaphyses at comparable dose levels and a given time. These results may serve as a reference for in vivo study design when rPTH or bPTH are to be the agents for studies on bone anabolism.

Journal Article↗

PubMed2000

Comparison of bisoprolol and carvedilol cardioprotection in a rabbit ischemia and reperfusion model.

Carvedilol, a selective alpha(1) and non-selective beta-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to the efficacy of carvedilol cardioprotection, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta(1) selective adrenoceptor antagonist, bisoprolol. Carvedilol (1 mg/kg) or bisoprolol (1 mg/kg) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (45 min) and reperfusion (240 min) resulted in significant increases in left ventricular end diastolic pressure, large myocardial infarction (64.7+/-2.6% of area-at-risk) and a marked increase in myeloperoxidase activity (64+/-14 U/g protein in area-at-risk). Carvedilol treatment resulted in sustained reduction of the pressure-rate-index and significantly smaller infarcts (30+/-2.9, P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (26+/-11 U/g protein in area-at-risk, P<0.01 vs. vehicle). Administration of bisoprolol at 1 mg/kg resulted in a pressure-rate-index comparable to that of carvedilol and also decreased infarct size (48.4+/-2.5%, P<0.001 vs. vehicle, P<0.05 vs. carvedilol), although to a significantly lesser extent than that observed with carvedilol. Treatment with bisoprolol failed to reduce myeloperoxidase activity in the ischemic myocardial tissue. In addition, carvedilol, but not bisoprolol, markedly decreased cardiac membrane lipid peroxidation measured by thiobarbituric acid formation. Taken together, this study suggests that the superior cardioprotection of carvedilol over bisoprolol is possibly the result of carvedilol's antioxidant and anti-neutrophil effects, not its hemodynamic properties.

Adrenergic beta-Agonists↗

PubMed2000

Presence of diverse human immunodeficiency virus type 1 viral variants in Cameroon.

Phylogenetic analysis of the gp41 region of 123 HIV-1-seropositive specimens from Cameroon showed that 89 were subtype A (71% of these sequences were IbNg-like), 12 (10%) were subtype D, 11 (9%) were subtype G, 5 (4%; closely related to subtype F2) were subtype F, 1 was subtype H, 2 (1.6%) remained unclassifiable, while 3 were group O. Further analysis of the two unclassifiable specimens in gag(p24), pol(prot), and env (C2V3 or gp41) showed that one (98CM19) was a complex mosaic between subtype A in p24 and subtype J prot, and unclassifiable in env (C2V3 or gp41). The second, 98CM63, clustered distinctly from all known subtypes in p24, prot, C2V3, or gp41. 98CM63 clustered with a specimen from Cyprus and these two geographically and epidemiologically unlinked specimens, with their distinct clustering pattern, may represent a new subcluster of subtype A. In conclusion, these findings confirm the high HIV-1 genetic variability and further suggest the continuous appearance of new viral strains in this population.

Amino Acid Sequence↗

PubMed2000

Molecular analysis of murine leukemia cell lines resistant to 5, 10-dideazatetrahydrofolate identifies several amino acids critical to the function of folylpolyglutamate synthetase.

Four L1210 murine leukemia cell lines resistant to 5, 10-dideazatetrahydrofolate (DDATHF) and other folate analogs, but sensitive to continuous exposure to methotrexate, were developed by chemical mutagenesis followed by DDATHF selective pressure. Endogenous folate pools were modestly reduced but polyglutamate derivatives of DDATHF and ALIMTA (LY231514, MTA) were markedly decreased in these mutant cell lines. Membrane transport was not a factor in drug resistance; rather, folypolyglutamate synthetase (FPGS) activity was decreased by >98%. In each cell line, FPGS mRNA expression was unchanged but both alleles of the FPGS gene bore a point mutation in highly conserved domains of the coding region. Four mutations were in the predicted ATP-, folate-, and/or glutamate-binding sites of FPGS, and two others were clustered in a peptide predicted to be beta sheet 5, based on the crystal structure of the Lactobacillus casei enzyme. Transfection of cDNAs for three mutant enzymes into FPGS-null Chinese hamster ovary cells restored a reduced level of clonal growth, whereas a T339I mutant supported growth at a level comparable to that of the wild-type enzyme. The two mutations predicted to be in beta sheet 5, and one in the loop between NH(2)- and COOH-terminal domains did not support cell growth. When sets of mutated cDNAs were co-transfected into FPGS-null cells to mimic the genotype of drug-selected resistant cells, clonal growth was restored. These results demonstrate for the first time that single amino acid substitutions in several critical regions of FPGS can cause marked resistance to tetrahydrofolate antimetabolites, while still allowing cell survival.

Amino Acid Sequence↗

PubMed2000

Association of an interleukin 1 alpha polymorphism with Alzheimer's disease.

BACKGROUND: Retrospective epidemiologic studies suggest that individuals exposed to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a lower probability of developing AD as well as an older age at onset for the illness. Neuroinflammation may play an important role in the pathogenesis of AD. Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized immunohistochemically to neuritic plaques, a requisite neuropathologic feature for AD. A polymorphism in the 5'-flanking regulatory region at -889 of the IL-1 alpha gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an overexpression of IL-1 alpha, a finding shown to be associated with inflammatory diseases. The IL-1A(-889) allele 2 polymorphism may be associated with AD pathogenesis. METHODS: A total of 259 patients with AD and 192 nondemented control subjects were included from two different centers (Indianapolis, IN, and Munich, Germany). Genotyping for APOE alleles and IL-1A(-889) allele 2 was performed by PCR-based amplification followed by restrictive endonuclease digestion. Statistical analyses were conducted by center-, gender group-, and age group-stratified Mantel-Haenszel odds ratios, CI, and p values. RESULTS: The allele frequency of IL-1A(-889) allele 2 was 46% in clinically diagnosed patients with probable AD versus 34% in control subjects from the combined centers. CONCLUSION: The authors found an increased risk for AD with an estimated Mantel-Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for IL-1A(-889) allele 2. They found no evidence for an interaction between the IL-1A and the apoE epsilon 4 polymorphisms (carriers and homozygotes), age, or gender with regard to conferred risk. The data strongly support an association between the IL-1A(-889) allele 2, especially in homozygotes, and later-onset AD.

Aged↗

PubMed2000

ElogPoct: a tool for lipophilicity determination in drug discovery.

We present an RP-HPLC method, for the determination of logPoct values for neutral drugs, which combines ease of operation with high accuracy and which has been shown to work for a set of 36 molecules comprised largely of drugs. The general features of the method are as follows: (i) compound sparing (< or = 1 mL of a 30-50 microg/mL solution needed), (ii) rapid determinations (20 min on average), (iii) low sensitivity to impurities, (iv) wide lipophilicity range (6 logPoct units), (v) good accuracy, (vi) excellent reproducibility. A linear free energy relationship (LFER) analysis, based on solvation parameters, shows that the method encodes the same information obtained from a shake-flask logPoct determination. To the best of our knowledge a similar performance, on a set of noncongeneric drugs, has not been previously reported. We refer to the value generated via this method as ElogPoct.

1-Octanol↗

PubMed2000

Phylogenetic analysis of protease and transmembrane region of HIV type 1 group O.

The molecular diversity and phylogenetic relationship of 22 HIV-1 group O strains were examined on the basis of the protease gene and the N-terminal region of gp41env. Analysis of the newly characterized protease sequences with 12 reference sequences revealed no specific clustering patterns, despite the distinct geographic locations of the specimens. In contrast, analysis of the newly sequenced gp41 sequences with 34 published sequences revealed two distinct clusters, each represented by one full-length sequence (MVP5180 and ANT-70). Further, four of the specimens classified as group O in the protease region clustered with group M in the gp41 region (three subtype A and one subtype G, respectively), suggesting dual and/or recombinant infections with HIV-1 groups M and O. The presence of two distinct clusters in the gp41 region indicates at least two possible subtypes within group O viruses, and this may provide useful information regarding molecular epidemiological studies of group O infections.

Amino Acid Sequence↗

PubMed2000

Functional architecture of synapses in the inner retina: segregation of visual signals by stratification of bipolar cell axon terminals.

We correlated the morphology of salamander bipolar cells with characteristics of their light responses, recorded under voltage-clamp conditions. Twelve types of bipolar cells were identified, each displaying a unique morphology and level(s) of axon terminal stratification in the inner plexiform layer (IPL) and exhibiting light responses that differed with respect to polarity, kinetics, the relative strengths of rod and cone inputs, and characteristics of spontaneous EPSCs (sEPSCs) and IPSCs. In addition to the well known segregation of visual information into ON and OFF channels along the depth of the IPL, we found an overlying mapping of spectral information in this same dimension, with cone signals being transmitted predominantly to the central IPL and rod signals being sent predominantly to the margins of the IPL. The kinetics of bipolar cell responses correlated with this segregation of ON and OFF and of rod and cone information in the IPL. At light offset, rod-dominated cells displayed larger slow cationic current tails and smaller rapid overshoot responses than did cone-dominated cells. sEPSCs were generally absent in depolarizing bipolar cells but present in all hyperpolarizing bipolar cells (HBCs) and larger in rod-dominated HBCs than in cone-dominated HBCs. Inhibitory chloride currents, elicited both at light onset and light offset, tended to be larger for cone-dominated cells than for rod-dominated cells. This orderly segregation of visual signals along the depth of the IPL simplifies the integration of visual information in the retina, and it begins a chain of parallel processing in the visual system.

Ambystoma↗

PubMed2000

Timing the ancestor of the HIV-1 pandemic strains.

HIV-1 sequences were analyzed to estimate the timing of the ancestral sequence of the main group of HIV-1, the strains responsible for the AIDS pandemic. Using parallel supercomputers and assuming a constant rate of evolution, we applied maximum-likelihood phylogenetic methods to unprecedented amounts of data for this calculation. We validated our approach by correctly estimating the timing of two historically documented points. Using a comprehensive full-length envelope sequence alignment, we estimated the date of the last common ancestor of the main group of HIV-1 to be 1931 (1915-41). Analysis of a gag gene alignment, subregions of envelope including additional sequences, and a method that relaxed the assumption of a strict molecular clock also supported these results.

Acquired Immunodeficiency Syndrome↗

PubMed2000

The reduced folate carrier in L1210 murine leukemia cells is a 58-kDa protein.

The reduced folate carrier (RFC1) is a major transporter for both natural reduced folates and antifolate chemotherapeutics. Using polyclonal antibodies targeted to epitopes at the loop between the sixth and seventh predicted transmembrane domains or the distal C-terminus, we were able to demonstrate by Western blot analysis that the molecular size of RFC1 expressed in murine leukemia L1210 cells is 58 kDa as predicted by the open reading frame of its cDNA. 46- and 38-kDa proteins detected only in plasma membrane preparations were proteolytic degradation products that appeared during membrane preparation or treatment with the conventional SDS-PAGE loading buffer. These data resolve discrepancies reported previously for the molecular size of RFC1.

Animals↗