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Biomedical subjects

Q Peng

Publications and source records attributed to Q Peng.

At least 109 records · Page 6Linked to original sources

Influenza A virus RNA polymerase subunit PB2 is the endonuclease which cleaves host cell mRNA and functions only as the trimeric enzyme.

The influenza A virus RNA-dependent RNA polymerase catalyzes several reactions in transcription and replication of the genome RNA. The first step in viral mRNA synthesis is the endonucleolytic cleavage of host cell mRNAs containing a cap structure to generate capped primers that are 10-14 nucleotides long which are then used to prime transcription of virus-specific mRNAs. To analyze the properties of the capped RNA-specific endonuclease associated with the influenza virus polymerase and the roles of each of the three subunits in transcription initiation, we established an in vitro assay to investigate this endonucleolytic cleavage reaction. This assay consists of an artificial RNA substrate containing a cap-0 structure at its 5' end and a partial alfalfa mosaic virus RNA 4 (AIMV RNA 4) sequence which had been shown to be cleaved by the influenza polymerase. Results showed that purified virion ribonucleoprotein complexes cleaved the RNA substrate specifically to generate a capped 14-nt RNA fragment for use as primer to initiate viral mRNA synthesis. Purified polyclonal anti-PB2 IgG inhibited the endonuclease activity, but anti-PB1 and anti-PA antibodies did not inhibit the cleavage. Partially purified trimeric polymerase expressed by recombinant baculovirus in insect cells cleaved the artificial substrate, but if one or two subunits were removed from the polymerase complex, the cleavage activity was totally lost. Our results suggest that viral PB2 protein is the endonuclease that cleaves host cell mRNA to produce the primer used to initiate transcription; however, association with the other two enzyme subunits seems to be required for this PB2 function.

Animals↗

The rise and prospects of medical aesthetics.

Since the 1980s, Chinese scholars have been trying to expound and synthetise elementary aesthetical ideas which occur in medicine, in order to treat this area of study as a defined branch of medicine--'medical aesthetics'. It is in this context that the points discussed in this paper arise. We set forth in detail the ideas, objectives and methods adopted within the framework of medical aesthetics and its applied branch--medical cosmetology and expound the relations between them. We think the task of medical aesthetics is to study the human body in its entirety, concentrating on both internal and external beauty and put the findings into practice, whereas the task of medical cosmetology is to study and assess only the external beauty of the human body and to take action on that basis. Medical cosmetology is the enforcement of medical aesthetics, practised in order to give positive results connected with physical beauty, and is therefore easily understood by the layman. It is known that the development of medical cosmetology represents an important breakthrough in the development of medical aesthetics. We think that beauty should not be measured mechanically, always following the same pattern, but that it should be considered individually with everyone's own particular characteristics. The quality of physical attractiveness should be assessed jointly by the doctor and his patient or client, not solely by either of these individuals nor even by a group of doctors.(ABSTRACT TRUNCATED AT 250 WORDS)

China↗

Correlation of distribution of sulphonated aluminium phthalocyanines with their photodynamic effect in tumour and skin of mice bearing CaD2 mammary carcinoma.

A chemical extraction assay and fluorescence microscopy incorporating a light-sensitive thermoelectrically cooled charge-coupled device (CCD) camera was used to study the kinetics of uptake, retention and localisation of disulphonated aluminium phthalocyanine (A1PcS2) and tetrasulphonated aluminium phthalocyanine (A1PcS4) at different time intervals after an i.p. injection at a dose of 10 mg kg-1 body weight (b.w.) in tumour and surrounding normal skin and muscle of female C3D2/F1 mice bearing CaD2 mammary carcinoma. Moreover, the photodynamic effect on the tumour and normal skin using sulphonated aluminium phthalocyanines (A1PcS1, A1PcS2, A1pcS4) and Photofrin was compared with respect to dye, dye dose and time interval between dye administration and light exposure. The maximal concentrations of A1PcS2 in the tumour tissue were reached 2-24 h after injection of the dye, while the amounts of A1PcS4 peaked 1-2 h after the dye administration. A1PcS2 was simultaneously localised in the interstitium and in the neoplastic cells of the tumour, whereas A1PcS4 appeared to localise only in the stroma of the tumour. The photodynamic efficiency (light was applied 24 h after dye injection at a dose of 10 mg kg-1 b.w.) of the tumours was found to decrease in the following order: A1PcS2 > A1PcS4 > Photofrin > A1PcS1. Furthermore, photodynamic efficacy was strongly dependent upon dye doses and time intervals between dye administration and light exposure: the higher the dose, the higher the photodynamic efficiency. The most efficient photodynamic therapy (PDT) of the tumour was reached (day 20 tumour-free) when light exposure took place 2 h after injection of A1PcS2 (10 mg kg-1). A dual intratumoral localisation pattern of the dye, as found for A1PcS2, seems desirable to obtain a high photodynamic efficiency. The kinetic patterns of uptake, retention and localisation of A1PcS2 and A1PcS4 are roughly correlated with their photodynamic effect on the tumour and normal skin.

Animals↗

Distribution of 5-aminolevulinic acid-induced porphyrins in noduloulcerative basal cell carcinoma.

Microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced porphyrins in 22 patients with a total number of 52 noduloulcerative basal cell carcinomas (BCC) after topical ALA application with or without dimethylsulfoxide (DMSO)/ethylenediaminetetraacetic acid (EDTA) or after intravenous administration of ALA. Both localization patterns and amounts of ALA-induced porphyrins in the BCC were studied. The ALA-induced porphyrins were localized only in the superficial layers of the noduloulcerative BCC lesions after topical application of 20% ALA alone for 3 h. However, both the penetration of ALA into deep lesions and the production of the ALA-induced porphyrin fluorescence were increased after topical administration of 20% ALA and 20% DMSO/4% EDTA for 3 h. Prior treatment with 99% DMSO for 15 min further enhanced the ALA penetration into the BCC lesions after topical application of the ALA/DMSO/EDTA mixture and produced more ALA-induced porphyrins by a factor of about three compared with those treated with ALA alone. The penetration of ALA into the deep BCC lesions could also be increased by prolonging the time of topical application of 20% ALA/4% EDTA to 29-48 h (without DMSO). Intravenous injection of ALA led to a more homogeneous distribution of the ALA-derived porphyrins in the whole noduloulcerative BCC lesions.

Adult↗

The use of near-infrared charge-transfer transitions of low-spin ferric chlorins in axial ligand assignment.

The near-infrared magnetic circular dichroism spectra of some low-spin derivatives of ferric-octaethylchlorin substituted myoglobin have been recorded at cryogenic temperatures. The spectra, which include some of the lowest energy charge-transfer transitions ever observed for hemes, are clearly dependent upon the nature of the axial ligands present. While the results indicate that such spectra may have some practical utility in axial ligand assignment, as is now quite common practice for iron-porphyrin systems, there are some severe practical limitations to this protocol documented in the case of iron-chlorins.

Apoproteins↗

Pressure against the tumor can reduce the efficiency of photochemotherapy.

C3D2/F1 mice with mammary carcinoma tumors growing subcutaneously on their right foot were given 10 mg/kg aluminium phthalocyanine tetrasulfonate (AlPcS4) by intraperitoneal injection. Twenty-four hours later these tumors were exposed to light at 680 nm. The size of the tumors was measured daily. An exposure of 135 J/cm2 (150 mW/cm2) reduced the tumor growth rate so that the time needed for the tumors to reach a volume five times larger than that at the time of exposure increased from 4 days for control tumors to 15 days. However, when a glass plate was gently pressed against the tumor surface during irradiation, the effect of an identical exposure was significantly smaller. In agreement with this, microscopic studies showed that tumors exposed to laser light without any pressure applied during irradiation were more damaged than tumors receiving a slight pressure. Thus, pressure against the tumor can obviously reduce the oxygen concentration in this tumor enough to reduce the efficiency of the treatment.

Animals↗

Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in alpha beta(+) T cells.

Through cognate B-cell-T-cell interactions and provision of cytokines, CD4+ T-cell antigen receptor (TCR) alpha beta+ T cells regulate immunoglobulin isotype synthesis. Murine IgG1 and IgE secretion is therefore substantially T-cell-dependent, whereas IgM and IgG3 secretion is not. Here we report that in the absence of alpha beta T cells, B cells expand, differentiate and secrete copious amounts of antibodies of 'T-dependent' isotypes. Moreover, the antibodies are reactive towards self-antigens, as in patients with systemic lupus erythematosus, so autoantibodies of 'T-dependent' type can develop without the help of CD4+ alpha beta T cells. This phenotype is not evident in mice or humans that are congenitally deficient in specific alpha beta T-cell functions, but bears comparison with B-cell hyperactivity and autoimmunity in transplant rejection and in immunodeficiencies such as AIDS.

Animals↗

Identification of axial ligands of cytochrome c552 from Nitrosomonas europaea.

Cytochrome c552 from Nitrosomonas europaea was analyzed by visible, EPR and MCD spectroscopies. The visible and MCD data show that histidine and methionine are the axial ligands to the heme iron of the ferric protein. The EPR spectrum of the cytochrome shows an atypical highly axial low spin (HALS) type signal with g-values that make it difficult to identify the axial ligands. These results reinforce the value of near-infrared MCD spectroscopy for assigning ligands in ferric heme systems and point out the difficulties in using only EPR spectroscopy for the same purpose. The description of another c-cytochrome exhibiting a HALS-type EPR signal will eventually be helpful in explaining the physical basis for this unusual signal.

Circular Dichroism↗

Anticomplement activity in human aqueous humor.

Twenty-six samples of human aqueous humor from patients with cataract and glaucoma were analyzed on anticomplement activity. The mean inhibitory rate was 15.32 +/- 14.60%, ranging from 0.93 to 60.02%. The inhibitory effect appeared in a dose-dependent manner. No significant differences were found between males and females (p > 0.05) and between samples of different age (p > 0.05). We revealed that aqueous humor had an inhibitory effect on complement activity. This indicates that human aqueous humor has an immune regulatory function.

Adult↗

Uptake and distribution of intravenously or intravesically administered photosensitizers in the rat.

Photodynamic therapy using i.v. injected porphyrin photosensitizers have been used to treat selected cases of superficial bladder cancer. Since cutaneous photosensitivity, lasting 6-8 weeks, is a well known undesirable side effect of this therapy, we instilled the photosensitizers intravesically in rats and compared the uptake of photosensitizers in different tissues by this route of administration with the uptake after intravenous injection. The intravesical mode of delivery enhanced photosensitizer uptake in the bladder wall, while giving low concentrations in extravesical organs. Intravesical instillation of the photosensitizers may therefore increase their efficacy and reduce phototoxicity as compared with intravenous injection. Comparing the results obtained by two assays, one based on porphyrin fluorescence and the other based on the application of radioactively labelled photosensitizers, it was concluded that the i.v. administration route may result in tissue uptake of significant amounts of aggregated non-fluorescent, supposedly inactive drug, while the intravesical administration led to less uptake of aggregates relative to active drug monomers.

Animals↗

Biodistribution of a methylene blue derivative in tumor and normal tissues of rats.

By using a chemical extraction procedure and confocal laser scanning fluorescence microscopy we have investigated the kinetic patterns of uptake and biolocalization of a methylene blue derivative (MBD) in tumors and various normal tissues of Wistar rats bearing fibrosarcoma (Leeds ovarian tumor) after intravenous injection of MBD (10 mg kg-1 body weight). Similar kinetics of accumulation and elimination of MBD fluorescence were found in tumor tissue and surrounding normal skin and muscle tissues. However, the tumor:skin and tumor:muscle ratios of the MBD fluorescence intensity were found to be 9 and 4, respectively, 4 h after intravenous injection, indicating selective uptake of MBD by the tumor tissue. MBD was localized on the walls of all the vessels and extensively in the area of neoplastic cellular and tumorigenic fibrous components in the tumor tissue. Interestingly, no MBD fluorescence could be detected in the metastatic neoplastic cells in the remote lymph nodes. In the skin, MBD was mainly distributed in the keratinized epithelium of the epidermis, hair follicles and their accessories, while little was found both in the epidermis and dermis. In most other tissues, the maximal fluorescence intensity of MBD was found 1-4 h after injection, after which it decreased dramatically to almost undetectable levels 120 h postinjection. Strong fluorescence of MBD was seen in the tracheal mucosal epithelium, while little fluorescence was noted in the transitional epithelium of bladder. The kinetics of biolocalization of MBD in some other tissues (liver, spleen, kidney, brain, muscle, lung, heart) were also studied.

Animals↗

Tissue carriers for processing fragile bio-materials in immuno-electron microscopy.

The preparation and use of tissue carriers for processing fragile biological materials from postfixation up to embedding in electron microscopy is described. Trimmed small pieces of vibratome sections can be very practical and safely transported in these carriers throughout osmification, dehydration for long times, and infiltration up to embedding in epoxy resins. This small device is especially suited for post-embedding immunogold electron microscopy.

Animals↗

A new technique for post-embedding immunogold localization of vasopressin in the rat median eminence.

A modified cryosubstitution method is described which simultaneously preserves the ultrastructure and antigenicity of the osmium-sensitive neuropeptide vasopressin in rat median eminences. The organs were aldehyde-fixed, osmicated, and embedded in Epon. Thin sections were no longer needed to be etched and the titer of primary antiserum was near to the light microscopic level. Furthermore ice crystallization could not be observed.

Animals↗

Potentiation of photodynamic therapy by mitomycin C in cultured human colon adenocarcinoma cells.

The effects of photodynamic therapy (PDT) alone and in combination with Mitomycin C (MMC) on WiDr cells, a human colon adenocarcinoma cell line, were investigated. The addition of MMC increased the cytotoxicity of PDT. The presence of MMC resulted in a reduction or a removal of the shoulder of the PDT survival curves as well as an increase in their slopes. Increasing with the concentrations of MMC from 0.01 to 0.025 micrograms/ml, the cytotoxic effects of the two treatments changed from additivity to supra-additivity as judged by comparing dose-response curves for each treatment alone with survival curves after combination therapy and by isobologram analysis. The cytotoxicity of MMC could also be enhanced by a practically nontoxic treatment of PDT (8% cell inactivation). The cytotoxicities of MMC and PDT in combination were found to be dependent on the sequence of the two treatments. When MMC (> or = 0.02 micrograms/ml) and Photofrin II were given simultaneously for 16 h and then followed by irradiation, the combination was found to be more effective than when MMC was given to the cells immediately after PDT and kept in the medium for 16 h. Possible mechanisms of the combination effects of PDT and MMC are discussed briefly.

Adenocarcinoma↗

Distribution and photosensitizing efficiency of porphyrins induced by application of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma.

By means of a chemical extraction procedure and confocal laser scanning microscopy, we investigated the kinetic patterns of uptake and biolocalization of 5-aminolevulinic acid (ALA)-induced porphyrins in s.c. transplanted tumors, adjacent normal skin and muscle, and liver of mice bearing mammary carcinoma, after i.p. injection of 250 mg/kg ALA or topical application of ALA (20% in an oil-in-water emulsion). Furthermore, we evaluated the tumor responses after either i.p. injection or topical application of 5-ALA followed by laser irradiation (632 nm, 150 mW/cm2, 25 min) by measuring the treated tumor regression/regrowth time and by light and electron microscopy. Strong fluorescence of ALA-induced porphyrins was detected in the tumor, skin and liver tissues, while little fluorescence was seen in the adjacent muscle tissue. Moreover, the highest amounts of ALA-induced porphyrins in the tumor and skin tissues were found 1 hr after i.p. injection, whereas the amounts of the porphyrins in both tissues increased with increasing time after topical application of ALA. The fluorescence of the porphyrins was localized in several components of the skin tissue (epidermis, hair follicles and their associated sebaceous glands). Furthermore, the fluorescence was diffusely distributed in the s.c. transplanted tumor tissue. Little could be observed under a confocal laser scan microscope (CLSM) in the muscle tissue. The uptake and biolocalization data correlate well with the results of PCT efficiency of the same tumor model with ALA-induced porphyrins. Light and electron microscopy showed that the mitochondria of the tumor cells and of the endothelial cells and the basal lamina of vascular walls beneath the endothelium in the tumor tissue were initially extensively destroyed after PCT with ALA-induced porphyrins. Thereafter, diffuse degeneration followed by local and/or diffuse severe necrosis of the tumor cells was found. This may be due mainly to the initial damage to mitochondria in the cancerous and endothelial cells and also to the destruction of the vascular wall in the tumor tissue.

Aminolevulinic Acid↗

Identification of heme macrocycle type by near-infrared magnetic circular dichroism spectroscopy at cryogenic temperatures.

The electron paramagnetic resonance (EPR) and near-infrared magnetic circular dichroism (MCD) spectra of the azide and cyanide adducts of nitrimyoglobin and hydroperoxidase II from Escherichia coli have been measured at cryogenic temperatures. For the first time, ligand-to-metal charge-transfer transitions in the near-infrared have been observed for an Fe(III)-chlorine system. It is shown that near-ultraviolet-to-visible region electronic spectra of 'green' hemes such as these are an unreliable indicator of macrocycle type. However, the combined application of EPR and near-infrared MCD spectroscopies clearly distinguishes between the porphyrin-containing nitrimyoglobin and the chlorine-containing hydroperoxidase II.

Circular Dichroism↗

Effects of light exposure on the uptake of photofrin II in tumors and normal tissues.

DBA mice bearing CaD2 mammary carcinomas were used to determine the effect of giving small doses of light to the tumor area 1.5 hr after injecting Photofrin II (PII). The smallest light dose applied (12.5 J/cm2) had no effect on the uptake of PII in the tumor and its surrounding tissues, as measured 24 hr after the i.p. injection. However, several higher light doses increased the uptake of PII in the tumor significantly, the uptake in skin slightly, while the uptake in muscle tissue was decreased rather than increased. Thus, the PII concentration ratio between the tumor and the surrounding normal tissues was significantly improved. The rates of clearance of PII from irradiated tissues and non-irradiated tissues were not significantly different. Most likely, the present observations are due to transient pH lowering in the tumor resulting from vascular damage.

Animals↗

Effect of mitomycin C on the uptake of photofrin II in a human colon adenocarcinoma cell line.

Flow cytometry (FCM) was used to investigate the effect of mitomycin C (MC) on the cellular uptake of Photofrin II (PII) in a cultured human colon adenocarcinoma cell line (WiDr). The surface area of the cells increased as they passed through the cell cycle from G0/G1 to G2/M phase. MC retarded the cells in G2/M phase and enhanced the surface area of the cells. A 1.3-2.3-fold increase in the cell surface area and a 1.3-2.7-fold increase in the cellular uptake of PII in the tumor cells was observed after 2 h-8 h incubation with MC. Within each sample, an almost linear relationship between the intensity of PII fluorescence in the cells and the surface area of the cells was found. However, for the cells incubated with MC the surface area was not the only determinant of PII uptake. Effects of MC on the cell cycle, the cell surface area and the permeability of the cell membrane are suggested as possible reasons for the increase of cellular uptake of PII in the tumor cells.

Adenocarcinoma↗