Analysis of budding yeast kinases controlled by DNA damage.
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Amino Acid Sequence↗
Biomedical subjects
M Huang
Publications and source records attributed to M Huang.
Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands.
Ninety-one cases of adenoid cystic carcinoma (ACC) of the salivary glands with more than ten years' follow up were studied to investigate factors influencing the survival rate of patients, which vary according to site, histological type, clinical stage and nature of therapy. The data were statistically analysed for survival curves. Log rank tests were employed to assess the statistical significance of various groups. As a result, it may be concluded that tumour site, clinical stage and histological type are the important factors influencing the prognosis. ACC of the palate and parotid, early clinical stage, glandular/tubular histological type, and tumour without nerve involvement had the best prognosis. ACC in the submandibular gland, maxillary antrum and tongue, advanced clinical stage (stage III and IV), solid histological type, and tumour with nerve involvement had a poor prognosis.
Adult↗
Azodicarbonamide inhibits HIV-1 replication by targeting the nucleocapsid protein.
Nucleocapsid p7 (NCp7) proteins of human immunodeficiency virus type 1 (HIV-1) contain two zinc binding domains of the sequence Cys-(X)2-Cys-(X)4-His-(X)4-Cys (CCHC). The spacing pattern and metal-chelating residues (3 Cys, 1 His) of these nucleocapside CCHC zinc fingers are highly conserved among retroviruses. These CCHC domains are required during both the early and late phases of retroviral replication, making them attractive targets for antiviral agents. toward that end, we have identified a number of antiviral chemotypes that electrophilically attack the sulfur atoms of the zinc-coordinating cysteine residues of the domains. Such nucleocapside inhibitors were directly virucidal by preventing the initiation of reverse transcription and blocked formation of infectious virus from cells through modification of CCHC domains within Gag precursors. Herein we report that azodicarbonamide (ADA) represents a new compound that inhibits HIV-1 and a broad range of retroviruses by targeting the the nucleocapsid CCHC domains. Vandevelde et al. also recently disclosed that ADA inhibits HIV-1 infection via an unidentified mechanism and that ADA was introduced into Phase I/II clinical trials in Europe for advanced AIDS. These studies distinguish ADA as the first known nucleocapsid inhibitor to progress to human trials and provide a lead compound for drug optimization.
Anti-HIV Agents↗
Multicomponent gene therapy vaccines for lung cancer: effective eradication of established murine tumors in vivo with interleukin-7/herpes simplex thymidine kinase-transduced autologous tumor and ex vivo activated dendritic cells.
Multiple antitumor modalities may be necessary to overcome lung tumor-mediated immunosuppression and effectively treat non-small cell lung cancer (NSCLC). To evaluate a multimodality gene therapy approach for control of local tumor growth, a weakly immunogenic murine alveolar cell carcinoma, L1C2, was transduced with either the interleukin-7/hygromycin-herpes simplex thymidine kinase (IL-7/HyHSVtk) internal ribosome entry site (IRES) retroviral vector or a vector containing the HyHSVtk, but not the IL-7 gene. Of the many cytokines available for gene transfer, IL-7 was chosen for these studies because it both stimulates CTL responses and down-regulates tumor production of the immunosuppressive peptide TGF-beta. Following selection in hygromycin, IL-7 transduction was confirmed by ELISA. Clones produced 1.25 to 10 ng of IL-7/ml/10(6) cells per 24 h. In vitro, genetically modified tumor cells were significantly more sensitive to ganciclovir (GCV) than unmodified parental tumor cells. The in vivo growth of ex vivo modified L1C2 cells was evaluated. There was a dose-response relationship between the amount of IL-7 secreted in vitro and the growth of genetically modified murine tumor in vivo. Transduced tumor cells regressed in mice following GCV therapy. Although ex vivo gene modification of tumor cells led to complete resolution of the tumor following implantation in vivo, IL-7 and HSVtk gene modified tumor cells were not effective in treating established parental tumors. However when 5 x 10(5) bone marrow-derived, in vitro activated dendritic cells (DC) were administered in combination with transduced tumor and GCV, 5 day old established tumors were eradicated in 80% of mice. These studies suggest that multicomponent vaccines may facilitate improved host responses by replacing host immune deficits and thus could have a role in adjuvant therapy and local control of NSCLC.
Animals↗
Anisotropy of human muscle via non-invasive impedance measurements.
Combining non-invasive 50 kHz impedance measurements with a mathematical model for the underlying structure, we obtain in vivo values for the transverse and longitudinal conductivities of the muscles of the human thigh and for the (isotropic) conductivity of the covering skin-fat layer. Results for a healthy male subject are in acceptably good agreement with those obtained elsewhere on surgically exposed or freshly excised animal tissue and with 'global' measurements on humans. Also, measurements using rotatable probes reveal orientations of underlying muscle fibres via minima in resistance versus angle curves. The results suggest potentially useful methods for studying muscle properties in clinical and physiological research.
Adipose Tissue↗
Maximum entropy method for magnetoencephalography.
Simulations show that the maximum entropy method is a promising technique for image reconstruction in magnetoencephalography. An algorithm based on the work of Skilling and Bryan [1] and an appropriately modified expression for the "entropy" is shown to provide high-quality reconstructions of both isolated and dense distributions of neural current "dipoles", neglecting return currents. In particular the results are substantially superior to those obtained with the well-known minimum norm procedure.
Artifacts↗
Characterization of human immunodeficiency virus type 1 matrix revertants: effects on virus assembly, Gag processing, and Env incorporation into virions.
The matrix protein of human immunodeficiency virus type 1 (HIV-1) has been postulated to serve a variety of functions in the virus life cycle. Previously, we introduced a large number of mutations into the HIV-1 matrix and determined the effects on virus replication. These studies identified domains involved in virus assembly and release and envelope glycoprotein incorporation into virions. Here we describe the identification and characterization of viral revertants containing second-site changes in the matrix which compensate for the effects of four of the original mutations on matrix function. Specifically, mutations at matrix residues 4 and 6 severely impaired virus assembly and release; substitutions at residues 4 and 6 reversed the phenotype of the amino acid 4 change while second-site mutations at matrix positions 10, 69, and 97 partially or fully reversed the phenotype of the amino acid 6 substitution. A mutation at matrix residue 62 reversed the effect of a position 34 change which blocks envelope glycoprotein incorporation into virions, and substitutions at residues 27 and 51 reversed the phenotype of a position 86 mutation which redirects virus assembly to the cytoplasm. In addition to determining the effects of the compensatory changes in the context of the original mutations, we also introduced and analyzed the second-site changes alone in the context of the wild-type molecular clone. The data presented here define potential intermolecular and intramolecular interactions which occur in the matrix during the virus life cycle and have implications for our understanding of the relationship between matrix structure and function.
Amino Acid Sequence↗
Incorporation of Pr160(gag-pol) into virus particles requires the presence of both the major homology region and adjacent C-terminal capsid sequences within the Gag-Pol polyprotein.
The determinants critical for the incorporation of Pr160(gag-pol) into human immunodeficiency virus type 1 (HIV-1) particles were examined by cotransfecting cells with (i) a plasmid expressing wild-type Gag protein and (ii) a series of chimeric Gag-Pol expression plasmids in which individual murine leukemia virus (MLV) Gag regions and subdomains precisely replaced their HIV-1 counterparts. The presence of the MLV MA and NC Gag regions in the chimeric Gag-Pol precursor had no detectable effect on the incorporation of Gag-Pol into progeny virions. In contrast, the entire HIV-1 CA region was required to achieve wild-type levels of Gag-Pol assembly into particles; both the CA major homology region and the adjacent C-terminal CA sequences play dominant roles in this process yet, when assayed in the context of a chimeric Gag-Pol polyprotein, restored the defect affecting Gag-Pol incorporation to approximately half of the wild-type level.
Capsid↗
Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae.
Ribonucleotide reductase (RNR), which catalyzes the rate-limiting step for deoxyribonucleotide production required for DNA synthesis, is an alpha2beta2 tetramer consisting of two large and two small subunits. RNR2 encodes a small subunit and is essential for mitotic viability in Saccharomyces cerevisiae. We have cloned a second essential gene encoding a homologous small subunit, RNR4. RNR4 and RNR2 appear to have nonoverlapping functions and cannot substitute for each other even when overproduced. The lethality of RNR4 deletion mutations can be suppressed by overexpression of RNR1 and RNR3, two genes encoding the large subunit of the RNR enzyme, indicating genetic interactions among the RNR genes. RNR2 and RNR4 may be present in the same reductase complex in vivo, since they coimmunoprecipitate from cell extracts. Like the other RNR genes, RNR4 is inducible by DNA-damaging agents through the same signal transduction pathway involving MEC1, RAD53, and DUN1 kinase genes. Analysis of DNA damage inducibility of RNR2 and RNR4 revealed partial inducibility in dun1 mutants, indicating a DUN1-independent branch of the transcriptional response to DNA damage.
Amino Acid Sequence↗
[An investigation of precipitation of airborne fungi particles in the rooms of university library].
Precipitation of airborne fungi particles in the rooms of an University library and the influencing factors were studied in May 1994 with the fallen plate method. The total average precipitation of airborne fungi particles was 11.68 per dish in 5 minutes. The differences were significant from different room patterns, floors and times, so were the humidity assayed. The book-store rooms and reading rooms had an average precipitation of 15.01 and 8.35 per dish in 5 minutes respectively (P < 0.05), and humidity of 41.7 and 11.4 percent respectively (P < 0.01). The influencing factors were: different floors and room patterns, the people's activity, the different time, humidity, ventilation and book pollution.
Air Microbiology↗
[Effects of habenula nucleus lesion on estrus cycle and fertility in the adult female rats].
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Animals↗
[The effects of E2 and it's metabolites on the proliferation of rat anterior pituitary cells in vitro].
OBJECTIVE AND METHODS: The present work is determined to observe the effects of E2 (estradiol), 2-OHE1 (2-hydroxyestrone), 2-OHE2 (2-hydroxyestrodiol) on the proliferation of rat anterior pituitary cells (APC) in vitro by laser scanning confocal microscopy. RESULTS: 10(-6) mol/L E2 stimulated the growth of APC. After 2 days of incubation with E2, the DNA content of APC increased to 1.3 times of the control group (P < 0.01). 10(-6) mol/L 2-OHE2 (other than 2-OHE1) stimulated proliferative activity of APC and inhibited the inhibitory effect of peribidil (10(-5) mol/L), a dopamine receptor agonist, on the poliferative activity of rat APC.
Animals↗
[Effects of calcium inhibitor on hydrogen peroxide-induced damage and calcium influx in bovine aortic endothelial cells in culture].
Hydrogen peroxide(H2O2)-induced cell damage and Ca2+ influx into bovine aortic endothelial cells (BAEC) were investigated. Our data suggested that H2O2 could dose- and time-dependently induce damage in cultured BAEC assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and increase malondialdehyde (MDA) production, which reflects the level of lipid peroxidation. Exposure of BAEC to H2O2 (100 mumol.L-1) caused significant increase in intracellular free calcium ([Ca2+]i) within 6 min, suggesting that the increase of [Ca2+]i might implicate in H2O2-induced cell damage. The calcium inhibitor nifedipine was found to dose-dependently decrease the increase of [Ca2+]i caused by H2O2 and protect BAEC against H2O2-induced damage reflected by significant decrease of MDA production and increase of MTT value. These results indicate that overload of calcium might be responsible to some extent causing oxidative damage to cells.
Animals↗
[Cord blood plasma selectively stimulates the expansion of hematopoietic pregenitor cells in vitro].
OBJECTIVE: To explore the effect of cord blood (CB) plasma on the expansion of hematopoietic progenitor cells. METHODS: The effect of CB plasma on the expansion of CB and bone marrow (BM)-derived hematopoietic progenitor cells was studies and compared with those of adult's peripheral blood (PB) plasma and cytokines such as IL-3 and SCF. RESULTS: (1) CB plasma increased CFU yields of CB-derived progenitor cells by 2.23 +/- 0.52-fold and this expansion was dependent on CB plasma concentrations supplemented in the cultures. Greater expansion of progenitor cells was found when ABO was unmatched between the CB-derived cells and CB plasma. (2) Stimulating effect of CB plasma on BM-derived progenitor cells was also related to ABO type. CFU yields were increased by 1.55 +/- 0.43-fold when ABO was unmatched and not increased when ABO was matched. (3) Expansion of CB-derived progenitor cells by IL-3 and SCF was revealed. Significant increase in CFU yields occurred in the addition of both the cytokine and the CB plasma. (4) No expansion occurred in CB-and BM-derived cell cultures supplemented with PB plasma. CONCLUSION: There is factor(s) selectively stimulating expansion of progenitor cells in CB plasma. It may be beneficial that CB plasma was transfused with CB-derived stem cell transplantation.
Animals↗
A 964 bp repetitive DNA in Entamoeba histolytica is associated with linear "chromosomal" DNAs of variable sizes.
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Animals↗
Two genes for PPi-dependent phosphofructokinase in Entamoeba histolytica.
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Animals↗
[Postsurgical changes of the calculated wall shear stress in autogenous interpositional venous grafts by blood flow waveform analysis: clinical and experimental studies].
This investigation was designed to evaluate the postsurgical changes of autogenous, interpositional venous grafts in terms of the calculated wall shear stress by blood flow waveform analysis. In a model of tethered elastic tube, mean wall shear stress (tau) was obtained by the following equation: tau = 32 microQ/(pi.D3). Twenty-four grafts in repairing limb arterial injuries from 24 patients were examined with Doppler ultrasonic image instrument (7.5 MHz) for follow-up studies. Three mongrel dogs were selected for experimental studies. A segment of femoral vein (4-5 cm) was excised, reversed and interpositionally grafted into the femoral artery. The mean wall shear stress was calculated at 1 hour, 24 hours, 1 week, 4 and 12 weeks after implantation. Two occluded grafts were demonstrated in one femoral and one popliteal artery. The value of mean wall shear stress was higher in upper limb group (over 1.1 N/m2) than in lower limb group (five over 1.1 N/m2 and seven below 1.1 N/m2). The value of mean wall shear stress of grafts with follow-up time of more than 24 weeks was over 1.1 N/m2 in 6 grafts including one from lower limb while that was below 1.1 N/m2 in 6 grafts (all from lower limbs). No significant difference was found between the mean flow velocity values in upper and lower groups. The results from the experiment revealed that the value of mean wall shear stress decreased at one hour after operation, and increased and reached a fixed value beyond 1 week postsurgery. The vein graft in upper limb has better early and long-term result than that in lower limb because wall shear stress is correlated with the intimal hyperplasia, then the outcome of autogenous vein graft. In conclusion, we propose that wall shear stress be applied for follow-up studies on vascular grafts in limb arterial injuries and hemodynamic factors be considered for arterial reconstructive procedures.
Adolescent↗
Non-small cell lung cancer-derived soluble mediators and prostaglandin E2 enhance peripheral blood lymphocyte IL-10 transcription and protein production.
Studies suggest that IL-10 may contribute to tumor-associated immunosuppression. In the current study we evaluated the capacity of human non-small cell lung cancer (NSCLC) cell lines to induce PBL IL-10 production. We observed a 10- to 100-fold increase in human PBL IL-10 production following exposure to NSCLC cell supernatants. The tumor-induced increase in PBL IL-10 production was partially blocked by pretreatment of the tumors with the PG inhibitor indomethacin. NSCLC lines were found to constitutively produce PGE2. Exogenous PGE2 also induced PBL IL-10 production in a dose- and time-dependent manner. Both PGE2 and NSCLC supernatant-induced PBL IL-10 production were due to an increase in the IL-10 mRNA transcriptional rate. To evaluate the significance of tumor-induced lymphocyte IL-10 production, the capacity of PBL to produce IFN-gamma during culture in tumor supernatants was assessed in the presence of specific anti-IL-10 mAb. We found enhanced PBL IFN-gamma production following anti-IL-10 treatment. These in vitro studies imply that NSCLC-induced PBL IL-10 production may serve to shift the Th1/Th2 cytokine axis at the tumor site and thus inhibit cell-mediated anti-tumor immune responses. These findings identify a mechanism by which lung cancer cells may escape host immune surveillance. We conclude that NSCLC-derived soluble mediators, including PGs, may play an immunoregulatory role through induction of lymphocyte IL-10 production.
Carcinoma, Non-Small-Cell Lung↗