Biomedical subjects

G Zhao

Publications and source records attributed to G Zhao.

At least 73 records · Page 4Linked to original sources

PubMed2001

Antihypertension and anti-cardiovascular remodeling by phenylalanine in spontaneously hypertensive rats: effectiveness and mechanisms.

OBJECTIVE: To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). METHODS: The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR-phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3H-thymidine counts per minute (cpm) incorporated into the new synthesized desoxyribonucleic acid (DNA) and determining the cell number with the crystal violet stain technique. The Ca2+ influx was measured in counts/min of 45CaCl2 after incubating it with 5 different concentrations of phenylalanine and the intracellular [Ca2+]i by Fura-II/Am indicator. The total messenger ribonucleic acid (mRNA) of the myocardium was extracted and Northern blot analysis was performed with the probe collagen alpha 2 (I) cDNA. The tyrosine hydroxylase (TH) activity was measured by high-performance liquid chromatography (HPLC) with electrochemical detector after having reacted with its substrate tyrosine and other reagents. The catecholamine contents in brain homogenat were detected by HPLC method. The comparison of pharmacokinetics of phenylalanine among SHR-phe, SHRs and control Wistar Kyoto (WKY) rats was made after intravenous injection of 3H-L-phe (1 ml/kg) by PK-GRAPH Program for kinetic calculation. The 3H-L-phe uptake by CSMCs after incubating for definite intervals was also detected and compared. RESULTS: Phenylalanine could prevent the increase of BP with ages and the heart weight (heart/body weight index). The aortic media thickness and the collagen content in the myocardium were decreased significantly in SHR-phe. Whereas the dearranged cardiovascular structure was much improved. The mechanisms might be direct and specific inhibition of the DNA synthesis and proliferation of cardiovascular cells which may be related to the inhibition of collagen alpha 2(I) cDNA, c-fos and c-myc expression. Other mechanisms may include decrease of intracellular [Ca2+]i and an inhibition of central sympathetic activity due to the results of higher TH activity in the caudate nucleus and higher adrenaline content in the posterior hypothalamus. Besides, partial recovery of phenylalanine metabolic aberrants existed in SHRs seems to be another possibility for its effectiveness. CONCLUSIONS: Phenylalanine intervention could exert a definite anti-hypertension and anti-cardiovascular remodeling effects on SHRs like seen in human essential hypertension. Its mechanisms might be related to direct inhibition of growth in the cardiovascular cells, decrease of central sympathetic activity, the reverse of the exhibited phenylalanine metabolic aberrants in SHRs, and a decrement of intracellular [Ca2+]i.

Animals↗

PubMed2001

Inherited disturbances of phenylalanine metabolic kinetics in essential hypertension.

OBJECTIVE: To clarify whether the disturbances in metabolic kinetics of the essential aminoacid, phenylalanine (phe), are implicated in the genetic pathogenesis of essential hypertension (EH). METHODS: 1. L-(2, 3D3)-leucine, L-(2, 3D3)-isoleucine, L-15N-lysine, L-(2, 3D3)-valine and L-(2, 3D3)-phe were used for simultaneously studying comparative metabolic kinetics using stable isotope tracer methods with a GC-MS system. Study groups were the offspring with both parents suffering EH (n = 10, FH+), 2 or more than 2 parents and grand-parents with EH and stroke (n = 12, FS+) and those without genetic predisposition of EH and stroke (n = 12, F) groups. 2. By comparing the radioactive counts of [3H]-phe, and their weight transformation in blood after 1.5 Ci/kg i.v. administration at defined intervals and in tissues obtained after being sacrified among spontaneously hypertensive rats (SHR), 2 kidney-1 clip hypertensive rats (2K1C) and their normotensive controls (WKY). 3. The time transport and concentration transport of [3H]-L-phe in cpm between the cultured vascular smooth muscle cell of 5th generation in SHR and WKY were compared. RESULTS: A single and unique disturbance of metabolic kinetics in phe were found in FH+, FS+ and SHR. The plasma pool or apparent volume of distribution was enlarged, and the turnover rate constants between plasma and cell tended to show a decrease. The pharmacokinetics of phe in 2K1C was not changed. Only phe content in heart and aorta, the vital organs for predicting BP, were higher in SHR than in WKY tissues studied. Both the time and concentration transport were higher in SHR, e.g., an increment in the net-uptake of L-phe by vascular tissue. CONCLUSION: A unique aberrant of metabolic kinetics of phe might be implicated in the inherited pathogenesis of EH and stroke both from clinical and animal studies.

Adult↗

PubMed2001

Ocular histopathological changes after eyeball enucleation induced by corneal trauma.

OBJECTIVE: To observe the ocular histopathological changes after eyeball enucleation induced by corneal trauma. METHODS: Light microscopic examination was done on 117 eyeball specimens enucleated after corneal trauma (18 with corneal fissure and 99 with corneal perforating trauma). RESULTS: Acute, subacute or chronic inflammatory changes, and fibrous membrane formation were observed in well-closed corneal wounds, whereas inflammation, atrophy and scar were observed in the focal tissues. But at the late period, secondary glaucoma, retinal detachment, endophthalmitis and eyeball atrophy resulted in blindness. Corneal fistula was observed in those with inadequate cure of wounds caused by ingrowth of corneal epithelium, embedment of iris and vitreous body, and large area of centrally located tissue deficiency of the corneal. A high incidence of endophthalmitis was noted due to the presence of corneal fistula. Severe inflammation was observed in the anterior segmental tissues with fibrous infiltration in the anterior chamber, which might result in rapid destruction of the eyeballs. CONCLUSIONS: Ocular pathology varies with the difference of the position, form, size and closing conditions of the corneal laceration after trauma.

Adolescent↗

PubMed2001

[A pathological study of lens subcapsular epithelial proliferation].

OBJECTIVE: To observe the histopathological changes of lens subcapsular epithelial proliferation and analyze their etiology. METHODS: Sixty-four enucleated eyes with lens subcapsular epithelial proliferation were observed with light microscopy and analyzed retrospectively. Among all the cases of lens subcapsular epithelial proliferation, there were 36 ones enucleated because of trauma, 10 absolute glaucoma, 6 corneoscleral staphyloma, 5 intraocular tumor, 2 after cataract extraction, 4 endophthalmitis, 1 cataract combined with ocular atrophy (diabetes type II). RESULTS: Proliferated lens subcapsular epithelial cells were atypical, irregularly arranged, and extended to the posterior subcapsule. In cases with lens capsular rupture or partial absence, there were subcapsular fibro-connective tissue metaplasia, scar tissue formation, cortical collapse, local liquefaction and calcification. CONCLUSION: Lens subcapsular epithelial proliferation is caused by some intraocular pathological conditions. In cases with endophthalmitis and ocular trauma, its severity is the most serious.

Adolescent↗

PubMed2001

[IR studies on hydrogen bonding in hard segment domains of segmented polyester polyurethaneurea].

Hydrogen bonding in hard segment domains of segmented polyester polyurethaneurea (PUU) based on 4,4'-diphenylmethane diisocyanate (MDI), ethylene diamine (ED) and polybutylene adipate (PBA) (M.W.1,975 and M.W.1,228) was studied by means of IR spectroscopy. It was found that the double peak absorption of urea C=O groups occurred in the studied PUU with the increase of hard segment content. Two hydrogen bonding models of urea C=O groups in different hard segment sequence lengths of PUU were proposed. Three dimensional hydrogen bonding in hard segment domains can be formed by further bonding of the above planar hydrogen bondings.

Hydrogen Bonding↗

PubMed2001

[IR studies on deuterated polyester polyurethaneurea elastomers].

Segmented polyester polyurethaneurea (PUU) based on 4,4'-disphenylmethane diisocyanate (MDI), ethylene diamine (ED) and polybutylene adipate (PBA) elastomers and their deuterated polymers were studied by means of IR spectroscopy. The results indicated that IR bands of hydrogen bonded N-H vibrations involved in PUU were greatly affected by deuteration. The bands which were sensitive to deuteration were those near 3,332, 3,190, 1,600, 1,539, 1,317, 1,257 and 1,230 cm-1, respectively. In addition, it was also found that PUU samples with different hard segment contents and polyester soft segment molecule weights were similarly affected by deuteration in degree.

Elasticity↗

PubMed2001

[IR studies on segmented polyester polyurethaneurea elastomers].

The studies segmented polyester polyurethaneurea (PUU) elastomers based on 4,4'-diphenylmethane diisocyanate (MDI), ethylene diamine (ED) and polybutylene adipate(PBA) (M.W.1,975 and M.W.1,228) were studied by means of IR spectrascopy. The major IR bands of PUU were first assigned and the views were proposed for the bands at 1,600, 1,317, 1,520 and 1,230 cm-1 assigned by other authors. The reliable theoretical basis for the assignments of IR bands and the studies of hydrogen bonding in these elastomers has been proposed by use of deuteration and varying temperature. The results indicated that substantial hydrogen bonding mainly occurred in the aggregate region of hard segments, a small amount of hydrogen bonding can be formed at the interface between the soft and hard segments. It can be concluded from this work that the studied PUU materials were phase segregation.

Elastomers↗

PubMed2001

[Transposition of pedicled adrenal gland for the treatment of adrenal medullary hyperplasia].

OBJECTIVE: To investigate the operative modes for adrenal medullary hyperplasia. METHODS: 8 cases of adrenal medullary hyperplasia were treated with transposition of pedicled adrenal gland. The inferior and the medial blood vessel of adrenal gland were ligated. The superior blood vessel of adrenal gland was formed a 5.0- 6.0 cm pedicle and dragged to the subcutaneous of dorsum. RESULT: After follow-up for an average of 2 years, only 1 of the 8 patients did not recover as a result of psychosis and others had no symptoms but normal endocrine results. CONCLUSION: Transposition of the pedicled adrenal gland is a simple and satisfied way to treat patients with adrenal medullary hyperplasia.

Adrenal Glands↗

PubMed2000

Inactivation of monomeric sarcosine oxidase by reaction with N-(cyclopropyl)glycine.

Monomeric sarcosine oxidase (MSOX) catalyzes the oxidative demethylation of sarcosine (N-methylglycine) and contains covalently bound flavin adenine dinucleotide (FAD). The present study demonstrates that N-(cyclopropyl)glycine (CPG) is a mechanism-based inhibitor. CPG forms a charge transfer complex with MSOX that reacts under aerobic conditions to yield a covalently modified, reduced flavin (lambda(max) = 422 nm, epsilon(422) = 3.9 mM(-1) cm(-1)), accompanied by a loss of enzyme activity. The CPG-modified flavin is converted at an 8-fold slower rate to 1,5-dihydro-FAD (EFADH(2)), which reacts rapidly with oxygen to regenerate unmodified, oxidized enzyme. As a result, CPG-modified MSOX reaches a CPG-dependent steady-state concentration under aerobic conditions and reverts back to unmodified enzyme upon removal of excess reagent. No loss of activity is observed under anaerobic conditions where EFADH(2) is formed in a reaction that goes to completion at low CPG concentrations. Aerobic denaturation of CPG-modified enzyme yields unmodified, oxidized flavin at a rate similar to the anaerobic denaturation reaction, which yields 1,5-dihydro-FAD. The CPG-modified flavin can be reduced with borohydride, a reaction that blocks conversion to unmodified flavin upon removal of excess CPG or enzyme denaturation. The possible chemical mechanism of inactivation and structure of the CPG-modified flavin are discussed.

Aerobiosis↗

PubMed2000

Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma.

Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.

Aged↗

PubMed2000

Crystal structure of Streptococcus pneumoniae acyl carrier protein synthase: an essential enzyme in bacterial fatty acid biosynthesis.

Acyl carrier protein synthase (AcpS) catalyzes the formation of holo-ACP, which mediates the essential transfer of acyl fatty acid intermediates during the biosynthesis of fatty acids and lipids in the cell. Thus, AcpS plays an important role in bacterial fatty acid and lipid biosynthesis, making it an attractive target for therapeutic intervention. We have determined, for the first time, the crystal structure of the Streptococcus pneumoniae AcpS and AcpS complexed with 3'5'-ADP, a product of AcpS, at 2.0 and 1.9 A resolution, respectively. The crystal structure reveals an alpha/beta fold and shows that AcpS assembles as a tightly packed functional trimer, with a non-crystallographic pseudo-symmetric 3-fold axis, which contains three active sites at the interface between protomers. Only two active sites are occupied by the ligand molecules. Although there is virtually no sequence similarity between the S.pneumoniae AcpS and the Bacillus subtilis Sfp transferase, a striking structural similarity between both enzymes was observed. These data provide a starting point for structure-based drug design efforts towards the identification of AcpS inhibitors with potent antibacterial activity.

Acyl Carrier Protein↗

PubMed2000

Biochemical and molecular analyses of the Streptococcus pneumoniae acyl carrier protein synthase, an enzyme essential for fatty acid biosynthesis.

Acyl carrier protein synthase (AcpS) is an essential enzyme in the biosynthesis of fatty acids in all bacteria. AcpS catalyzes the transfer of 4'-phosphopantetheine from coenzyme A (CoA) to apo-ACP, thus converting apo-ACP to holo-ACP that serves as an acyl carrier for the biosynthesis of fatty acids and lipids. To further understand the physiological role of AcpS, we identified, cloned, and expressed the acpS and acpP genes of Streptococcus pneumoniae and purified both products to homogeneity. Both acpS and acpP form operons with the genes whose functions are required for other cellular metabolism. The acpS gene complements an Escherichia coli mutant defective in the production of AcpS and appears to be essential for the growth of S. pneumoniae. Gel filtration and cross-linking analyses establish that purified AcpS exists as a homotrimer. AcpS activity was significantly stimulated by apo-ACP at concentrations over 10 microm and slightly inhibited at concentrations of 5-10 microm. Double reciprocal analysis of initial velocities of AcpS at various concentrations of CoA or apo-ACP indicated a random or compulsory ordered bi bi type of reaction mechanism. Further analysis of the inhibition kinetics of the product (3',5'-ADP) suggested that it is competitive with respect to CoA but mixed (competitive and noncompetitive) with respect to apo-ACP. Finally, apo-ACP bound tightly to AcpS in the absence of CoA, but CoA failed to do so in the absence of apo-ACP. Together, these results suggest that AcpS may be allosterically regulated by apo-ACP and probably proceeds by an ordered reaction mechanism with the first formation of the AcpS-apo-ACP complex and the subsequent transfer of 4'-phosphopantetheine to the apo-ACP of the complex.

Acyl Carrier Protein↗

PubMed2000

Refinement of the locus for autosomal dominant hereditary gingival fibromatosis (GINGF) to a 3.8-cM region on 2p21.

Hereditary gingival fibromatosis (HGF, MIM 135300; approved gene symbol GINGF) is an oral disease characterized by enlargement of gingiva. Recently, a locus for autosomal dominant HGF has been mapped to an 11-cM region on chromosome 2p21. In the current investigation, we genotyped four Chinese HGF families using polymorphic microsatellite markers on 2p21. The HOMOG test provided evidence for genetic homogeneity, with evidence for linkage in four families (heterogeneity versus homogeneity test HOMOG, chi(2) = 0. 00). A cumulative maximum two-point lod score of 5.04 was produced with marker D2S390 at a recombination frequency of θ = 0 in the four linked families. Haplotype analysis localized the hereditary gingival fibromatosis locus within the region defined by D2S352 and D2S2163. This region overlaps by 3.8 cM with the previously reported HGF region. Single-strand conformation polymorphism and sequence analysis of the coding region of cytochrome P450 1B1 (CYP1B1) excluded it as a likely candidate gene.

Aryl Hydrocarbon Hydroxylases↗

PubMed2000

A novel application of cyclosporine A in nonmyeloablative pretransplant host conditioning for allogeneic BMT.

The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on day -5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI) on day 0, allows fully major-histocompatibility-complex-mismatched allogeneic bone marrow engraftment and the induction of immunologic tolerance. TI is required in this model to overcome alloreactivity and possibly to make "space" in the recipient thymus so that lasting central tolerance can be achieved. In addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and glucocorticoids have a powerful influence on the thymus. In this study, we evaluated whether the administration of CYA to recipient mice for 12 days prior to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a combination of both, could create space and overcome alloresistance in the thymus by specifically depleting immature and mature thymocytes prior to BMT. High levels of multilineage donor hematopoietic repopulation and specific transplantation tolerance were achieved in mice treated from days -15 to -3 with CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day -5, followed by 3 Gy WBI and 15 x 10(6) allogeneic bone marrow cells on day 0. Vbeta analysis suggested a central deletional tolerance mechanism. The same treatment without CYA pretreatment allowed only transient chimerism, without tolerance. Corticosteroid treatment abolished the engraftment-promoting and tolerance-inducing effects of CYA. These results demonstrate a novel pretransplantation-only application of CYA, which facilitates allogeneic marrow engraftment with minimal conditioning, by creating thymic space and/or overcoming intrathymic alloresistance.

Animals↗

PubMed2000

Electrical transport in the ferromagnetic state of manganites: small-polaron metallic conduction at low temperatures.

We report measurements of the resistivity in the ferromagnetic state of epitaxial thin films of La(1-x)Ca(x)MnO3 and the low-temperature specific heat of a polycrystalline La0.8Ca0.2MnO3. The resistivity below 100 K can be well fitted by rho-rho(0) = Eomega(s)/sinh (2)(hs/ 2k(B)T) with h(omega)(s)/k(B) approximately 80 K and E being a constant. Such behavior is consistent with small-polaron coherent motion which involves a relaxation due to a soft optical phonon mode that is strongly coupled to the carriers. The specific-heat data also suggest the existence of such a phonon mode. The present results thus provide evidence for small-polaron metallic conduction in the ferromagnetic state of manganites.

Journal Article↗

PubMed2000

China's forest policy for the 21st century.

A half-century policy of forest exploitation and monoculture in China has led to disastrous consequences, including degradation of forests and landscapes, loss of biodiversity, unacceptable levels of soil erosion, and catastrophic flooding. A new forest policy had been adopted in China called the Natural Forest conservation Program (NFCP), which emphasizes expansion of natural forests and increasing the productivity of forest plantations. Through locally focused management strategies, biodiversity and forest resources will be sustained, and downstream regions will be better protected from flooding. This new policy is being implemented with a new combination of policy tools, including technical training and education, land management planning, mandatory conversion of marginal farmlands to forest, resettlement and retaining of forest dwellers, share in private ownership, and expanded research. These policy tools may have wider relevance for other countries, particularly developing countries.

Agriculture↗

PubMed2000

Differential sensitivity of rat hippocampal and cortical astrocytes to oxygen-glucose deprivation injury.

Selective vulnerability of hippocampal neurons to ischemia is felt to relate to intense glutamatergic input and glutamate receptor expression. Since astrocytes are thought to have a neuroprotective role we speculated that hippocampal astrocyte sensitivity to insult could also contribute to this regional vulnerability. The purpose of the study was to determine if there is a differential sensitivity of cultured hippocampal and cortical astrocytes to oxygen-glucose deprivation (OGD). Hippocampal and cortical astrocytes were grown to confluence at matching cell density. Cultures were exposed to OGD for 2, 4, 6, 8 and 10 h. Progressive reduction in viability occurred in hippocampal astrocytes beginning at 2 h OGD. Reduction in cortical astrocyte viability was not observed until 4 h OGD. Death of hippocampal astrocytes was significantly greater than that of cortical astrocytes at each period of OGD. Based on acid phosphatase activity data the LD(50) for OGD duration in hippocampal astrocytes was 2 h compared to 8 h in cortical astrocytes. Regional differences in sensitivity of astrocytes to OGD implies that this may contribute to regional differences in neuronal vulnerability to ischemia.

Acid Phosphatase↗

PubMed2000

Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro.

Several CNS disorders feature microglial activation. Microglia are known to have both restorative and cytotoxic capabilities. Neuronal apoptosis has been noted after an acute insult such as ischemia. Microglia may participate in this event. We previously showed that conditioned medium (CM) harvested from peritoneal macrophages or from activated microglia triggered apoptosis in rat hippocampal neurons in culture. We wished to characterize the factor responsible for triggering neuronal death. Quiescent microglia produced CM that did not disrupt hippocampal neurons. Lipopolysaccharide-activated microglia produced CM which resulted in neuronal death. This effect was blocked by plasminogen activator inhibitor-1, by tPA STOP, and by co-incubation with tPA antibody. Recombinant human tPA exaggerated the neurotoxic effects of microglial CM, while tPA alone was toxic only at very high concentrations. This in vitro system, which probably excludes any significant impact of microglial free radicals, suggests that microglial tPA may contribute significantly to hippocampal neuronal death.

Animals↗