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Biomedical subjects

G Gao

Publications and source records attributed to G Gao.

At least 55 records · Page 3Linked to original sources

Regulation of tumor cell apoptotic sensitivity during the cell cycle (Review).

Understanding how current chemotherapeutic modalities induce apoptosis is critical to designing better anti-cancer agents. This review is concerned with how pharmacological agents induce tumor cell apoptosis in a cell cycle-dependent manner. Recent experiments demonstrate that expression of several apoptotic regulatory proteins (such as Bcl-2, Bax, p53, and Survivin) are differentially regulated according to the phases of the cell cycle. This cell cycle-dependent regulation in turn contributes to increased drug sensitivity in different phases of the cell cycle. It is therefore likely that the cell cycle-dependent expression of cell death proteins plays a role in regulating chemosensitivity and apoptotic commitment of human tumor cells.

Antineoplastic Agents↗

[Laser-induced fluorescence (LIF) spectrum of colorectal cancer in vivo].

OBJECTIVE: To study the LIF spectrum of colorectal cancer, adenomas, chronic colitis and normal colon tissue in vivo, with special emphasis on precancerous lesions. METHODS: A nitrogen laser (wavelength 337 nm) beam was introduced through endoscopic colonoscope and the fluorescence emission was recorded. An optical multichannel analyzer (OMA III) was used to analyze the fluorescence emission spectrum. A total of 83 patients was examined. RESULTS: The emission spectrum of LIF recorded on colorectal cancer and normal tissue showed significant differences in intensity and shape. (1) The normal tissue had higher intensity than that of cancer tissue. (2) The main peak wavelength of cancer moved to the red. (3) The minor peak of the cancer tissue fell more slowly than that of the normal tissue. Intensity of the main peak (x1), intensity ratio of 400 to 530 nm (x2) and the integrated LIF intensity (350-600 nm) (x3) were used as parameters to obtain an equation. The sensitivity and specificity of LIF for diagnosis of colorectal cancer was 83.3% and 94.4%, respectively. In 87.1% of moderate and severe dysplastic adenomatous polyps, the fluorescence spectrum was abnormal. CONCLUSION: In vivo, the LIF spectrum can be used to distinguish colorectal cancer from normal colon, especially from dysplasia. It plays an important role in the early diagnosis of colorectal cancer.

Adult↗

[Study on beta 2 adrenergic receptor genetic polymorphisms in asthmatics in the people of the Han nationality of northern China].

OBJECTIVE: To analyze the association between beta 2-AR genetic polymorphism and asthma in the people of the Han nationality of northern China. METHODS: Allele Specific-PCR techniques were used to determine 16, 27 and 164 locus alleles of beta 2-AR genetic polymorphisms in 58 unrelated patients with asthma and 89 healthy controls from the people of the Han nationality of northern China. RESULTS: (1) The distribution frequency of genotype beta 2-AR 16 loci: Arg/Arg genotype accounts for 13%, Arg/Gly 76% and Gly/Gly 11%. The beta 2-AR 27 loci: Gln/Gln genotype accounts for 36%, Gln/Glu 55% and Glu/Glu 9%. The beta 2-AR 164 loci: Thr/Thr genotype accounts for 30%, Thr/Ile 53% and Ile/Ile 17%. (2) The frequency of genotype beta 2-AR 16 loci in asthmatics: Arg/Arg genotype accounts for 24%, Arg/Gly 45% and Gly/Gly 31%. There was a significant increase in the frequency of Gly/Gly genotype in asthmatics compared with healthy group(OR = 4.0, 95% CI 1.7-9.7), but there was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 27 loci in asthmatics: Gln/Gln genotype accounts for 34%, Gln/Glu 56% and Glu/Glu 10%. There was no significant difference in the allele frequency of asthmatics compared with healthy group. The frequency of genotype beta 2-AR 164 loci in asthmatics: Thr/Thr genotype accounts for 10%, Thr/Ile 83% and Ile/Ile 7%. There was no significant difference in the frequency of Ile/Ile genotype in asthmatics compared with healthy group, and in the allele frequency of asthmatics compared with healthy group. In addition, our study reveals that beta 2-AR 16 locus genetic polymorphism is in association with asthmatic severity. CONCLUSIONS: These results suggest that beta 2-AR 16 locus genetic polymorphism is correlated with asthma severity in the people of the Han nationality of northern China.

Adolescent↗

[A correlative study on the thyroid stimulating hormone levels between pregnant women and their newborns].

OBJECTIVE: The correlation between serum thyroid stimulating hormone (TSH) levels in pregnant women and their neonatal cord blood was explored. METHODS: With immunoradiometric assay (IRMA) technique, the serum TSH levels of 500 pregnant women and the cord blood TSH levels in the iodine deficiency areas (study group) were tested, while the TSH levels of 100 normal pregnant women and their newborns in iodine sufficient areas (control group) were compared. RESULTS: (1) In pregnant women, the mean serum TSH level in study group was significantly higher than that of control [(5.25 +/- 2.43) mU/L VS (4.69 +/- 1.34) mU/L, P < 0.01]. In newborns, the mean cord blood TSH level in study group was significantly higher than that of control (6.83 +/- 4.71) mU/L VS (5.32 +/- 3.02) mU/L, P < 0.001]. (2) The serum TSH levels in pregnant women were positively correlated with the cord blood TSH levels of their newborns in both groups. (3) The serum TSH levels of pregnant women was negatively correlated with their free triiodothy-ronine levels. CONCLUSION: The iodine nutrition status of newborns could be evaluated by monitoring the TSH levels of pregnant women.

Female↗

[Multivariate analysis of prognostic factors in renal cell carcinoma].

OBJECTIVE: To assess the effect of prognostic factors on renal cell carcinoma (RCC). METHODS: 316 cases of RCC were reviewed retrospectively. Their survival rates were calculated by Kaplan-Meier method and statistical differences were determined by Log-rank test. Significant prognostic factors were evaluated by Cox's multivariate proportional hazard model. RESULTS: After 40.3 +/- 18.5 month follow-up, the overall 5-year survival rate was 62.3%. By multivariate analysis, nine factors were included in Cox's multivariate proportional hazard model. M was the most important prognostic factor in RCC (P = 0.0013), and the others in turn were T (P = 0.0182), age (P = 0.0347), performance status (P = 0.0423), N (P = 0.0471), lymphadenectomy (P = 0.0542), grade (P = 0.0775), serum albumin (P = 0.1536), and serum creatinine (P = 0.4543). CONCLUSIONS: The significant prognostic factors in RCC were T, N, and M. Age and performance status showed the effect on prognosis of RCC. Lymph-node dissection also revealed a meaningful effect on relative lower stage of RCC.

Adult↗

[Analysis of the mental state of burn patients with postburn phobic neurosis].

OBJECTIVE: To analyze the mental state of burn patients with postburn neurosis, so as to pave the way for solving the problem. METHODS: The clinical symptoms and the mental states of forty-three burn patients with phobic neurosis were analyzed in terms of age, sex, severity of burn injury and methods of burn management in accordance with phobic objects. RESULTS: (1) Simple phobia and circumstance phobia were mainly found in children, whereas sick phobia and social phobia were in adults. (2) Phobic neurosis happened more often in female, especially those above 12 years old, than in male patients. (3) The burn injury severity was positively correlated with the incidence of phobic neurosis. (4) There was higher incidence of phobic neurosis in patients treated with bandaging than those with exposure method. CONCLUSION: It was very important to close burn wound as soon as possible, to correct deformity, to improve dysfunction, to perform cosmesis and plastic surgery and to rebuild patients self-esteem in order to prevent or decrease the incidence of postburn phobic neurosis.

Adolescent↗

[Study on the chemical form and extraction rate of Cr, Cu, Fe, Mn, Ni and Zn in tea].

The content of Cr, Cu, Fe, Mn, Ni and Zn in the tea commonly available in China market were measured by inductivity coupled plasma-optical emission spectrometry (ICP-OES). The extraction rates of the six elements in tea leachate were measured. The solubilitied were 39.8% for Cr, 42.5% for Cu, 8.6% for Fe, 45.5% for Mn, 87.1% for Ni and 71.0% for Zn. The process of making tea leachate affects the elements extraction rates. The content of the microelements in tea leave extracts decreases gradually with the processing. About 80% of Cr, Cu, Mn, Ni and Zn and 60% of Fe were in the first infusion of tea. Moreover, the chemical forms of six elements were determined. The ratios of organic to inorganic forms were 0.33 for Cr, 0.022 for Cu, 0.18 for Fe, 0.002 for Mn, 0.01 for Ni and 0.18 for Zn. It is concluded that the six elements from the tea infusion extracted from 5 g tea are too little to meet the recommend dietary allowance (RDA). Therefore, tea is not a rich food source of Cr, Cu, Fe, Mn, Ni and Zn.

Plant Extracts↗

Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in normal, malignant, and HTLV-I transformed human lymphocytes.

Intracellular cyclic AMP, determined in part by cyclic nucleotide phosphodiesterases (PDEs), regulates proliferation and immune functions in lymphoid cells. Total PDE, PDE3, and PDE4 activities were measured in phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC-PHA), normal natural killer (NK) cells, Jurkat and Kit225-K6 leukemic T-cells, T-cell lines transformed with human T-lymphotropic virus (HTLV)-I (a retrovirus that causes adult T-cell leukemia/lymphoma) and HTLV-II (a nonpathogenic retrovirus), normal B-cells, and B-cells transformed with Epstein-Barr virus (EBV). All cells exhibited PDE3 and PDE4 activities but in different proportions. In EBV-transformed B cells, PDE4 was much higher than PDE3. HTLV-I+ T-cells differed significantly from other T-lymphocyte-derived cells in also having a higher proportion of PDE4 activities, which apparently were not related to selective induction of any one PDE4 mRNA (judged by reverse transcription-polymerase chain reaction) or expression of the HTLV-I regulatory protein Tax. In MJ cells (an HTLV-I+ T-cell line), Jurkat cells, and PBMC-PHA cells, the tyrosine kinase inhibitor herbimycin A strongly inhibited PDE activity. Growth of MJ cells was inhibited by herbimycin A and a protein kinase C (PKC) inhibitor, and was arrested in G1 by rolipram, a specific PDE4 inhibitor. Proliferation of several HTLV-I+ T-cell lines, PBMC-PHA, and Jurkat cells was inhibited differentially by forskolin (which activates adenylyl cyclase), the selective PDE inhibitors cilostamide and rolipram, and the nonselective PDE inhibitors pentoxifylline and isobutyl methylxanthine. These results suggest that PDE4 isoforms may be functionally up-regulated in HTLV-I+ T-cells and may contribute to the virus-induced proliferation, and that PDEs could be therapeutic targets in immune/inflammatory and neoplastic diseases.

3',5'-Cyclic-AMP Phosphodiesterases↗

IL-3 and IL-4 activate cyclic nucleotide phosphodiesterases 3 (PDE3) and 4 (PDE4) by different mechanisms in FDCP2 myeloid cells.

In FDCP2 myeloid cells, IL-4 activated cyclic nucleotide phosphodiesterases PDE3 and PDE4, whereas IL-3, granulocyte-macrophage CSF (GM-CSF), and phorbol ester (PMA) selectively activated PDE4. IL-4 (not IL-3 or GM-CSF) induced tyrosine phosphorylation of insulin-receptor substrate-2 (IRS-2) and its association with phosphatidylinositol 3-kinase (PI3-K). TNF-alpha, AG-490 (Janus kinase inhibitor), and wortmannin (PI3-K inhibitor) inhibited activation of PDE3 and PDE4 by IL-4. TNF-alpha also blocked IL-4-induced tyrosine phosphorylation of IRS-2, but not of STAT6. AG-490 and wortmannin, not TNF-alpha, inhibited activation of PDE4 by IL-3. These results suggested that IL-4-induced activation of PDE3 and PDE4 was downstream of IRS-2/PI3-K, not STAT6, and that inhibition of tyrosine phosphorylation of IRS molecules might be one mechnism whereby TNF-alpha could selectively regulate activities of cytokines that utilized IRS proteins as signal transducers. RO31-7549 (protein kinase C (PKC) inhibitor) inhibited activation of PDE4 by PMA. IL-4, IL-3, and GM-CSF activated mitogen-activated protein (MAP) kinase and protein kinase B via PI3-K signals; PMA activated only MAP kinase via PKC signals. The MAP kinase kinase (MEK-1) inhibitor PD98059 inhibited IL-4-, IL-3-, and PMA-induced activation of MAP kinase and PDE4, but not IL-4-induced activation of PDE3. In FDCP2 cells transfected with constitutively activated MEK, MAP kinase and PDE4, not PDE3, were activated. Thus, in FDCP2 cells, PDE4 can be activated by overlapping MAP kinase-dependent pathways involving PI3-K (IL-4, IL-3, GM-CSF) or PKC (PMA), but selective activation of PDE3 by IL-4 is MAP kinase independent (but perhaps IRS-2/PI3-K dependent).

3',5'-Cyclic-AMP Phosphodiesterases↗

Novel organization and sequences of five genes encoding all six enzymes for de novo pyrimidine biosynthesis in Trypanosoma cruzi.

A 25 kb segment of genomic DNA from Trypanosoma cruzi, the causative agent of Chagas' disease, was sequenced. It contains five genes, pyr1, pyr2, pyr3, pyr4, and pyr6-5, encoding all six enzymes involved in de novo pyrimidine biosynthesis, glutamine-dependent carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, dihydroorotase, dihydroorotate dehydrogenase, and orotidine-5'-phosphate decarboxylase linked with orotate phosphoribosyltransferase, respectively. The pyr genes constitute a polycistronic transcription unit on an 800 kb chromosomal DNA in the order of pyr1, pyr3, pyr6-5, pyr2, and pyr4 from the 5' terminus, with intervening sequences of 2.2, 0.4, 8.1, and 0.8 kb. The amino acid sequences deduced from the trypanosomatid pyr genes, except for pyr6, showed closer similarities to mammalian and yeast sequences, and less similarity to archaeal and bacterial sequences. The last two enzymes encoded by a single gene, pyr6-5, are covalently linked in the order opposite to mammalian pyr5-6, and possess a putative glycosomal targeting signal tripeptide, serine-lysine-leucine, at the C terminus. The calculated isoelectric points of 9.3 and 9.9 are also diagnostic of the glycosomal localization of these enzymes. We conclude that the T. cruzi pyr gene organization represents an early progenitor in de novo pyrimidine biosynthesis in eukaryotic lineage, and that the independent pyr genes may have evolved before the gene fusion events that resulted in the three mammalian-type genes, pyr1-3-2, pyr4, and pyr5-6, for UMP synthesis. Peculiarities in the trypanosomatid pyr6-5 gene product are discussed.

Amino Acid Sequence↗

Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer.

Stable delivery of a therapeutic protein under pharmacologic control was achieved through in vivo somatic gene transfer. This system was based on the expression of two chimeric, human-derived proteins that were reconstituted by rapamycin into a transcription factor complex. A mixture of two adeno-associated virus vectors, one expressing the transcription factor chimeras and one containing erythropoietin (Epo) under the control of a promoter responsive to the transcription factor, was injected into skeletal muscle of immune-competent mice. Administration of rapamycin resulted in 200-fold induction of plasma Epo. Stable engraftment of this humanized system in immune-competent mice was achieved for 6 months with similar results for at least 3 months in a rhesus monkey.

Animals↗

Identification of coumarins from the fruit of Citrus hystrix DC as inhibitors of nitric oxide generation in mouse macrophage RAW 264.7 cells.

Three known coumarins have been isolated from Citrus hystrix DC as inhibitors of both lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) generation in RAW 264.7 cells. The inhibitory activity of bergamottin (IC(50) = 14 microM) was comparable to that of N-(iminoethyl)-L-ornithine (L-NIO) (IC(50) = 7. 9 microM), whereas oxypeucedanin and 5-[(6',7'-dihydroxy-3', 7'-dimethyl-2-octenyl)oxy]psoralen, structurally different from bergamottin only in their side-chain moieties, were notably less active. Using 21 coumarins, we structurally classified various types of coumarins into groups A-C: (A) bearing an isoprenyl (IP) or a geranyl (GR) group, highly active; (B) bearing an IP group cyclized to a coumarin ring, moderately active; (C) bearing an IP group modified with hydroxyl group(s) and/or having other functional groups except for the IP, completely inactive. Cellular uptake studies suggested that coumarins in group C are inactive because of poor permeability to the cell membrane.

Animals↗

Somatic cell mutants resistant to retrovirus replication: intracellular blocks during the early stages of infection.

To identify cellular functions involved in the early phase of the retroviral life cycle, somatic cell mutants were isolated after selection for resistance to infection. Rat2 fibroblasts were treated with chemical mutagens, and individual virus-resistant clones were recovered after selection for resistance to infection. Two clones were characterized in detail. Both mutant lines were resistant to infection by both ecotropic and amphotropic murine viruses, as well as by human immunodeficiency virus type 1 pseudotypes. One clone showed a strong block to reverse transcription of the retroviral RNA, including formation of the earliest DNA products. The second clone showed normal levels of viral DNA synthesis but did not allow formation of the circular DNAs normally found in the nucleus. Cell fractionation showed that the viral preintegration complex was present in a form that could not be extracted under conditions that readily extracted the complex from wild-type cells. The results suggest that the DNA was trapped in a nonproductive state and excluded from the nucleus of the infected cell. The properties of these two mutant lines suggest that host gene products play important roles both before and after reverse transcription.

Animals↗

Pneumolysin, a protein toxin of Streptococcus pneumoniae, induces nitric oxide production from macrophages.

Nitric oxide (NO) production by inducible NO synthase (iNOS) during inflammation is an essential element of antimicrobial immunity but can also contribute to host-induced tissue damage. Under conditions of bacterial sepsis, large amounts of NO are produced, causing hypotension, a critical pathological feature of septic shock. In sepsis caused by gram-positive organisms, the bacterial factors contributing to host NO production are poorly characterized. We show that a soluble toxin of Streptococcus pneumoniae, pneumolysin (Pln), is a key component initiating NO production from macrophages. In contrast to wild-type bacteria, a mutant of S. pneumoniae lacking Pln failed to elicit NO production from murine macrophages. Purified recombinant Pln induced NO production at low concentrations and independently of exogenous gamma interferon (IFN-gamma) priming of RAW 264.7 macrophages. However, IFN-gamma was essential for Pln-induced NO production, since primary macrophages from mice lacking the IFN-gamma receptor or interferon regulatory factor 1, a transcription factor essential for iNOS expression, failed to produce NO when stimulated with Pln. In addition, Pln acts as an agonist of tumor necrosis factor alpha and interleukin 6 production in macrophages. The properties of Pln, previously identified as a pore-forming hemolysin, also include a role as a general inflammatory agonist.

Animals↗

Gene therapy vectors based on adeno-associated virus type 1.

The complete sequence of adeno-associated virus type 1 (AAV-1) was defined. Its genome of 4,718 nucleotides demonstrates high homology with those of other AAV serotypes, including AAV-6, which appears to have arisen from homologous recombination between AAV-1 and AAV-2. Analysis of sera from nonhuman and human primates for neutralizing antibodies (NAB) against AAV-1 and AAV-2 revealed the following. (i) NAB to AAV-1 are more common than NAB to AAV-2 in nonhuman primates, while the reverse is true in humans; and (ii) sera from 36% of nonhuman primates neutralized AAV-1 but not AAV-2, while sera from 8% of humans neutralized AAV-2 but not AAV-1. An infectious clone of AAV-1 was isolated from a replicated monomer form, and vectors were created with AAV-2 inverted terminal repeats and AAV-1 Rep and Cap functions. Both AAV-1- and AAV-2-based vectors transduced murine liver and muscle in vivo; AAV-1 was more efficient for muscle, while AAV-2 transduced liver more efficiently. Strong NAB responses were detected for each vector administered to murine skeletal muscle; these responses prevented readministration of the same serotype but did not substantially cross-neutralize the other serotype. Similar results were observed in the context of liver-directed gene transfer, except for a significant, but incomplete, neutralization of AAV-1 from a previous treatment with AAV-2. Vectors based on AAV-1 may be preferred in some applications of human gene therapy.

Adolescent↗

[Studies on flavonoids from Aquilegia oxysepala Trautv. et Mey].

OBJECTIVE: To study the chemical constituents in Aquilegia oxysepala. METHOD: Various chromatographic techniques were used to separate and purify the constituents. The structures were determined by spectral analysis and chemical evidence. RESULT: Five flavonoids were isolated from the plant and identified as genkwanin, apigenin, luteonlin, swertisin and tilianin. CONCLUSION: All these compounds were isolated from the plant for the first time.

Apigenin↗

[Studies on chemical constituents of Thalictrum atriplex Finet et Gagnep].

OBJECTIVE: To study the chemical constituents in the aerial part of Thalictrum atriplex. METHOD: Chromatography and spectral analysis were used to isolate and elucidate the constituents. RESULT: Six compounds were isolated from the aerial part of Thalictrum atriplex, and elucidated as protocatechuic acid, caffeic acid, p-coumaric acid, kaempferol, beta-sitosterol and N-methylcorydaldine. CONCLUSION: They are all isolated from the plant for the first time.

Caffeic Acids↗