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Biomedical subjects

Q Peng

Publications and source records attributed to Q Peng.

At least 73 records · Page 4Linked to original sources

[Use of 5-aminolevulinic acid in photochemotherapy and fluorescence diagnostics].

5-aminolevulinic acid is an early intermediate product in the synthesis of heme. Some of the enzymes in the heme synthesis chain have altered activities in tumor tissue, so that application of 5-aminolevulinic acid leads to an accumulation of protoporphyrin IX in tumors. This molecule absorbs light and acts as a potent photosensitizer; tumors containing the compound can therefore be destroyed by light. 5-aminolevulinic acid based photochemotherapy is presently being employed in the treatment of thin basal cell carcinomas in many countries. The cosmetic result of this treatment is excellent. Furthermore, it is a simple and inexpensive form of treatment with curative rates comparable to those of established therapy modalities. Experimentally, a number of other malignant lesions reachable by light via optical fibers are being treated. Since protoporphyrin IX has a characteristic red fluorescence, 5-aminolevulinic acid can also be applied for diagnostic purposes.

Aminolevulinic Acid↗

Apoptosis induction by different pathways with methylene blue derivative and light from mitochondrial sites in V79 cells.

The importance of mitochondria for the induction of apoptosis by photodynamic therapy (PDT) was studied with a new photosensitizing dye, methylene blue derivative (MBD), and light. By using fluorescence microscopy and by measuring the MBD-PDT-induced inhibition of specifically subcellularly localized marker enzymes, we show that MBD is localized in mitochondria and not in lysosomes, endoplasmic reticulum or Golgi apparatus of V79 Chinese hamster fibroblasts. Cellular uptake kinetics and fluorescence properties of the dye in cells were characterized. Cell death was studied by a cell survival assay and by flow cytometry of cells stained using the terminal deoxynucleotidyl transferase (TdT) assay. MBD with light induced cell death by apoptosis via 2 different pathways, one rapid and one delayed, depending on the amount of dye in the cells. Cells treated with an MBD concentration higher than 0.05 microg/ml died by apoptosis within 3 hr after light exposure. At a concentration of 0.05 microg/ml MBD, cell death was induced slowly, and apoptotic cells appeared increasingly from the second day after PDT. Combination studies with 2-deoxyglucose (2-DOG) and carbonylcyanide-m-chlorophenylhydrazone (CCCP), inhibitors of glycolysis and oxidative phosphorylation, respectively, indicated that MBD and light inhibited mitochondrial oxidative phosphorylation. Abolishment of both energy sources led to cell death by necrosis within 6 hr. Inhibition of glycolysis alone induced apoptosis between 3 and 6 hr, while inhibition of mitochondrial oxidative phosphorylation alone led to delayed apoptosis within days.

Animals↗

Posterior capsular plaque: a common feature of cataract surgery in the developing world.

PURPOSE: To study the histopathologic findings of posterior capsular plaque, a lesion that is discovered frequently in eyes undergoing cataract surgery in the developing world. METHODS: Two hundred human crystalline lenses removed from 200 eyes of 200 patients who underwent intracapsular cataract extraction at Sagarmatha Choudhary Eye Hospital in Nepal were analyzed histopathologically. RESULTS: Forty-nine lenses (24.5%) had a posterior capsular plaque. We confirm that the posterior plaques are composed of collagen that stains positively for Masson trichrome stain and that forms after pseudofibrous metaplasia of lens cells along the posterior capsule. The plaques form in a fashion analogous to a healing process. CONCLUSIONS: We postulate that posterior capsular plaques result from posterior migration of epithelium and pseudofibrous metaplasia of lens epithelium. Most of the posterior capsular plaques are minute and not likely to affect vision. However, a small percentage of plaques are thicker and are likely to impair vision after extracapsular cataract surgery.

Adult↗

Fixation elements on plate intraocular lens: large positioning holes to improve security of capsular fixation.

OBJECTIVE: This study aimed to evaluate in rabbit eyes the effects of large positioning holes in one-piece silicone plate-haptic intraocular lenses (IOLs) with respect to security of capsular bag fixation. Mechanical strength of capsular fixation is correlated with the histologic findings of regenerating lens material and fibrous tissue ingrowth through the positioning holes on silicone plate IOLs, comparing capsules implanted with large-hole style plate IOLs to fellow capsules implanted with small-hole style plate IOLs. DESIGN: The study design was a prospective, randomized, experimental study. PARTICIPANTS: A total of 40 fellow capsular bags from 20 New Zealand white rabbits were examined. Capsules implanted with conventional small-hole silicone plate IOLs were used as the control in all pairs of fellow capsules. INTERVENTION: Phacoemulsification and implantation of a silicone plate IOL with small positioning holes in one eye and implantation of a silicone plate IOL with large positioning holes in the fellow eye were measured. All rabbits were killed at 2 months. The force required to extract the IOLs from the capsular bag was measured. All capsular bags underwent histopathologic analysis. MAIN OUTCOME MEASURES: Extraction force measurements and histopathologic examination, comparing capsules implanted with small-hole plate IOLs with fellow capsules implanted with large-hole plate IOLs, were measured. RESULTS: The large-hole style IOL required significantly more force to extract from the capsular bag compared to the conventional small-hole style (P = 0.003). Histologically, proliferating lens epithelial material and fibrous tissue were observed growing through all of the large positioning holes (synechia formation) but not through any of the small positioning holes. CONCLUSIONS: Silicone plate IOLs with large positioning holes become affixed more firmly within the capsular bag compared to conventional small-hole plate IOLs. These findings suggest that large holes in silicone plate IOLs allow for superior capsular bag fixation. This should reduce the rates of decentration and dislocation.

Animals↗

Fructus corni enhances endothelial cell antioxidant defenses.

1. The present study determined the effects of Fructus corni extract (FCE) on the levels of hydrogen peroxide (H2O2) and superoxide anion (O2-), on the glutathione (GSH) redox cycle and on the activities of antioxidant enzymes in bovine pulmonary artery endothelial cells (PAECs). 2. Confluent monolayers of PAECs were incubated with FCE, and oxidative stress was triggered by hypoxanthine and xanthine oxidase (to induce H2O2) or H2O2 (to induce O2-). 3. FCE exhibited a concentration-dependent suppression of H2O2 and O2-. 4. It modulated the GSH redox cycle by increasing the intracellular GSH content, the activities of GSH peroxidase and GSH disulfide reductase, and by decreasing the intracellular level of GSH disulfide. 5. It also increased the activities of superoxide dismutase and catalase. 6. These results demonstrate that FCE can promote a protective antioxidant defense state by affecting some important enzymatic and nonenzymatic oxidant-scavenging systems and may thus be useful for the prevention or treatment of disorders associated with oxidative damage.

Animals↗

Mini-haptics to improve capsular fixation of plate-haptic silicone intraocular lenses.

PURPOSE: To evaluate the effects of a new mini-haptic design on the strength and stability of capsular bag fixation of plate-haptic silicone intraocular lenses (IOLs) and determine whether this design encourages the growth of regenerating lens material or fibrous tissue around the haptic biomaterial and thus improves lens fixation in the capsular bag. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Department of Ophthalmology, Charleston, South Carolina, USA. METHODS: Six rabbits had bilateral continuous curvilinear capsulorhexis, phacoemulsification, and plate-haptic silicone IOL implantation. Each rabbit had a small-hole plate IOL (Chiron C10UB) implanted in the right eye and a mini-haptic plate IOL (Chiron C40UB) in the left eye. All rabbits were killed at 2 months. The force required to extract one haptic from the capsular bag was measured with a digital force gauge. Histopathologic analysis was performed on all specimens. RESULTS: The mini-haptic style IOLs required significantly more extraction force than the small-hole design (P = .011). Histopathologically, proliferating lens epithelial cells were observed growing circumferentially around the mini-haptics, causing a 360 degree synechia formation. This formation did not occur with the conventional small-hole plate IOLs used as the control. CONCLUSIONS: Lens epithelial cell proliferation around the mini-haptics significantly improved capsular bag fixation of the plate-haptic silicone IOL. This should decrease the incidence of clinical decentration and dislocation.

Animals↗

Fructus corni attenuates oxidative stress in macrophages and endothelial cells.

The antioxidant effect of a Chinese medicinal herb, Fructus corni extract (FCE), was investigated using models of oxidative stress in macrophages and vascular endothelial cells. Murine macrophages (J774) were incubated with FCE at 37 degrees C and 5% CO2 for 1 hr. Oxidative burst was triggered by zymosan and measured with a fluorescent probe. FCE exhibited a concentration- dependent suppression of oxidative burst. Confluent monolayers of bovine pulmonary artery endothelial cells (PAEC) were preincubated with FCE for 20 hrs, washed, and then exposed to an organic oxidant t-butyl hydroperoxide (tBHP) for 2 hrs. Cell viability was assessed by methylthiazol tetrazolium (MTT) assay, and cell injury by the release of intracellular lactate dehydrogenase (LDH). Lipid peroxidation products of PAEC were determined by measuring thiobarbituric acid-reactive substances (TBARS). Exposure of PAEC to tBHP resulted in decreased cell viability, increased LDH release, and elevated TBARS. Preincubation of PAEC with FCE significantly reversed these changes. Our results demonstrated that FCE can protect vascular endothelial cells from oxidant injury. The data thus suggest that Fructus corni may be useful for the prevention and/or treatment of disorders associated with oxidative damage.

Animals↗

[Genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase P1 and susceptibility to esophageal cancer].

OBJECTIVES: To study the association between genetic polymorphisms of cytochrome P4502E1 (CYP2E1) and/or glutathione S-transferase P1 (GSTP1) and susceptibility to esophageal cancer. METHODS: Genotyping of CYP2E1 and GSTP1 was performed using PCR-based RFLP analysis on DNA isolated from surgically removed esophageal tissues or scraped esophageal epithelium from cancer cases (n = 45), severe epithelial hyperplasia cases (n = 45), and normal controls (n = 45). RESULTS: The variant genotypes (c1/c2 and c2/c2) detected by RsaI digestion was found in 17% of epithelial hyperplasia cases, 20.0% of esophageal cancer cases and 55.6% of controls, with the differences being statistically significant (P < 0.001). Subjects carrying wild-type genotype of CYP2E1 had more than 5-fold risk for developing severe epithelial hyperplasia (odds ratio, OR = 5.78; 95% confidence interval, CI = 2.2-15.2) and esophageal cancer (OR = 5.00; 95% CI = 2.0-12.8). No association with the risk of severe epithelial hyperplasia and esophageal cancer was observed for the DraI polymorphism of CYP2E1 or for the Awl26I polymorphism of GSTP1. CONCLUSION: CYP2E1 is a genetic susceptibility factor involved in the early events for esophageal carcinogenesis.

Adult↗

[Deletion of MTS1/p16 gene in human esophageal carcinoma].

OBJECTIVE: To investigate the alteration of MTS1/p16 gene in human esophageal carcinoma. METHODS: A total of 60 human esophageal tissue specimens, comprising 30 squamous-cell carcinomas and 30 tumor-adjacent tissue specimens, were examined for homozygous deletion of p16 gene by using Southern blot hybridization and PCR method. RESULTS: The results showed that no deletions were detected in 30 tumor-adjacent tissue samples. However, of 30 esophageal carcinoma specimens, 7 were found negative for p16 gene in Southern blot assay, and the deletion of the p16 gene in 5 samples were confirmed by PCR with a 16.7% p16 gene deletion rate. CONCLUSION: These data suggest that MTS1/p16 gene alterations may play a role in the progression of human esophageal carcinoma.

Blotting, Southern↗

[FTIR study on the normal and tumor gastrointestinal tissues].

Series of cancer tissues and corresponding normal tissues of gastrointestinal tract (stomach, colon, esophagus) were studied by FTIR technique and the results showed the analogy of the spectra for the cancer tissues, while the spectra of normal tissues can be classified into three kinds. The secondary structures of protein were obtained by using deconvolution and curve-fitting techniques with Amide I bands and the results showed that the contents of alpha -helix and beta-sheet are different between the normal and cancer tissues.

Connective Tissue↗

Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1.

Genetic polymorphisms in enzymes involved in carcinogen metabolism have been shown to influence susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is primarily responsible for the bioactivation of many low molecular weight carcinogens, including certain nitrosamines, whereas glutathione S-transferases (GSTs) are involved in detoxifying many other carcinogenic electrophiles. Esophageal cancer, which is prevalent in China, is hypothesized to be related to environmental nitrosamine exposure. Thus, we conducted a pilot case-control study to examine the association between CYP2E1, GSTM1, GSTT1, and GSTP1 genetic polymorphisms and esophageal cancer susceptibility. DNA samples were isolated from surgically removed esophageal tissues or scraped esophageal epithelium from cases with cancer (n = 45), cases with severe epithelial hyperplasia (n = 45), and normal controls (n = 46) from a high-risk area, Linxian County, China. RFLPs in the CYP2E1 and the GSTP1 genes were determined by PCR amplification followed by digestion with RsaI or DraI and Alw26I, respectively. Deletion of the GSTM1 and GSTT1 genes was examined by a multiplex PCR. The CYP2E1 polymorphism detected by RsaI was significantly different between controls (56%) and cases with cancer (20%) or severe epithelial hyperplasia (17%; P < 0.001). Persons without the RsaI variant alleles had more than a 4-6-fold risk of developing severe epithelial hyperplasia (adjusted odds ratio, 6.0; 95% confidence interval, 2.3-16.0) and cancer (adjusted odds ratio, 4.8; 95% confidence interval, 1.8-12.4). Polymorphisms in the GSTs were not associated with increased esophageal cancer risk. These results indicate that CYP2E1 may be a genetic susceptibility factor involved in the early events leading to the development of esophageal cancer.

Adult↗

Potent induction of a neutrophil and eosinophil-rich infiltrate in vivo by human mast cell tryptase: selective enhancement of eosinophil recruitment by histamine.

Tryptase is the most abundant protein constituent of the secretory granules of human mast cells, but little is known of the contribution of this serine proteinase in acute allergic reactions. We have purified tryptase from human lung tissue by immunoaffinity procedures, and have investigated its potential to provoke an inflammatory infiltrate in vivo. Within 6 h of injection into the skin of guinea pigs, the accumulation of large numbers of neutrophils and eosinophils was observed, and those eosinophils closest to the injection site were partially degranulated. Similarly, injection of tryptase into the peritoneum of mice, even in quantities as low as 5 ng, stimulated the ingress of neutrophils. The response was dose dependent at 3, 6, and 16 h, with increases in median numbers of up to 400-fold. At the later time points eosinophil numbers were increased by up to 10-fold, and there were elevations also in the numbers of lymphocytes and macrophages. In both models, the actions of tryptase appeared to be dependent on an intact catalytic site. Coinjection of heparin with tryptase had relatively little effect on tryptase-induced responses. On the other hand, although histamine did not itself stimulate cell accumulation, over a range of concentrations it altered the cellular composition of the infiltrate induced by tryptase. Addition of histamine to tryptase provoked selective increases in eosinophil numbers of up to fivefold in the mouse peritoneum. Tryptase may provide an important stimulus for granulocyte recruitment in allergic disease.

Adjuvants, Immunologic↗

5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges.

BACKGROUND: Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25-years. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other than ALA-derived protoprophyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis. However, no review updating the clinical data has appeared so far. METHODS: A review of recently published data on clinical ALA-based PDT and diagnosis was conducted. RESULTS: Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results. However, the modality with present protocols does not in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors. Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases. Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain. The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs. CONCLUSIONS: Promising results of ALA-based clinical PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue: improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems.

Aminolevulinic Acid↗

Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture.

Human tumor cells of the lines WiDr (adenocarcinoma of the rectosigmoid colon), NHIK 3025 (carcinoma of the cervix), and V79 Chinese hamster fibroblasts were treated with 5-aminolevulinic acid (ALA) and ALA esterified to C1-C3 and C6-C8 chained aliphatic alcohols (ALA-esters). In the human cell lines, esterification of ALA with the long-chain (C6-C8) alcohols was found to reduce 30-150-fold the amount of ALA needed to reach the same level of protoporphyrin IX (PpIX) accumulation as with non-esterified ALA. The long-chained ALA-esters were less efficient in stimulating PpIX formation in V79 cells, i.e., the same amount of PpIX was formed by a 1-2.6-fold lower concentration of long-chained ALA-esters than with ALA. Short-chained ALA-esters (C1-C3) induced 5 to 10 times lower PpIX accumulation than ALA in all of the cell lines. High-performance liquid chromatography and fluorescence microscopic studies indicated that esterification of ALA has neither impact on the fluorescing porphyrin species formed nor impact on their intracellular localization. The PpIX formed from ALA-esters and ALA was found to be equally efficient in sensitizing cells to photoinactivation. The present results indicate that esterified ALAs are new and promising drugs for use in photochemotherapy of cancer.

Adenocarcinoma↗

Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX accumulation in tumours and normal tissues.

Laser-induced fluorescence (LIF) for in vivo point monitoring and fluorescence microscopy incorporating a CCD camera were used to study the fluorescence distribution of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) in tumours. Fluorescence in a chemically-induced adenocarcinoma in the liver of rats and in an aggressive basal cell carcinoma in a patient were studied after intravenous injection of ALA at a dose of 30 mg/kg body weight. The LIF technique demonstrated slightly more ALA-induced PpIX fluorescence in the tumour than in the surrounding normal liver and abdominal muscle of rats. The visible parts of the human basal cell carcinoma exhibited strong ALA-induced fluorescence, while this fluorescence was much weaker in the necrotic areas of the tumour and in the surrounding normal skin.

Adenocarcinoma↗

Anatomical study of the synovial plicae of the hip joint.

Observations and measurements of the synovial plicae of the hip joints were made on 63 embalmed cadavers. The cadavers were divided equally among three age groups (fetuses, children, and adults). Our observations showed that the plicae appeared in two forms (flat and villous) and were mainly confined to the external surface of the lower medial part of the acetabular labrum (labral plicae), the base of the ligament of the head of the femur (ligamental plicae), and along the reflecting line of the synovial membrane on the base of the femoral neck (neck plicae). The ligamental plicae were well padded with a fibroelastic pad of fat filling the acetabular fossa, and the neck plicae were far away from the articular surfaces of the joint; as a result, neither was likely to be injured or entrapped during joint movements. The labral plicae were larger than the ligamental or neck plicae and had an incidence of 73.8% in the fetal group. The fetal plicae were found only after the fetal age of 5 months. In nine cases of the child and adult groups, the labral plicae extended between the articular surface of the femoral head and the lower part of the acetabulum during medial rotation of the thigh. When the thigh was rotated laterally, the plicae in six of the same cases could be returned to their original positions. In the remaining three cases, there was continual impingement.

Adolescent↗

Security of capsular fixation: small-versus large-hole plate-hepatic lenses.

PURPOSE: To assess the effect of relatively large positioning holes on the security of capsular bag fixation of plate-haptic silicone intraocular lenses (IOLs). SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This study tested the hypothesis that larger holes allow ingrowth of lens material, fibrous tissue, or both through them, which helps fixate the lens more firmly in the capsular bag. Five rabbits had bilateral continuous curvilinear capsulorhexis, phacoemulsification, and implantation of a plate-haptic silicone IOL. An IOL with a small, round positioning hole (Staar AA-4203V) was implanted in the right eye in each rabbit, and a large-hole IOL (Staar AA-4203VF) was implanted in the left eye. After 2 months, all rabbits were killed. The force required to extract one haptic from the capsular bag was measured with a digital force meter. All eyes had histopathological analysis. RESULTS: It was slightly more difficult to extract a large-hole IOL from the capsular bag, although this trend was not statistically significant. However, histopathological analysis consistently showed 360 degree synechia formation through the holes, showing that the IOL could be securely fixed in position. CONCLUSIONS: Proliferation of lens epithelial cells through a large positioning hole in a plate-haptic silicone IOL may improve the long-term security of capsular bag fixation. This will help reduce the incidence of IOL decentration and dislocation.

Animals↗