Biomedical subjects

L Ma

Publications and source records attributed to L Ma.

At least 307 records · Page 17Linked to original sources

PubMed1998

Effects of Tripterygium wilfordii hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production.

OBJECTIVE: Extracts of the Chinese herbal remedy Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, but the mechanism of this therapeutic effect has not been completely delineated. The present study was designed to assess the effects of TWHF on the in vitro synthesis of prostaglandin E2 (PGE2) and on the expression of the cyclooxygenase isoforms, COX-1 and COX-2, in various human cell types. METHODS: Monocytes from human peripheral blood (HM), fibroblasts from rheumatoid arthritis synovial tissue (RASF), human neonatal foreskin fibroblasts (HFF), and the histiocytic cell line U937 were cultured for designated time periods with or without lipopolysaccharide (LPS), and in the presence or absence of varying concentrations of the following inhibitors: the methanol/chloroform (T2) extract of TWHF, the ethyl acetate (EA) extract of TWHF, a purified diterpenoid component of TWHF (triptolide), dexamethasone, and indomethacin. Culture supernatants were harvested for PGE2 content assays. Total RNA was extracted from the cells and analyzed for COX-1 and COX-2 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction or Northern blotting. RESULTS: Both the T2 and EA extracts inhibited PGE2 synthesis in the LPS-stimulated HM, RASF, and HFF cells, which was reflected by a marked suppression in the levels of mRNA for COX-2. In contrast, neither extract inhibited PGE2 production in U937 cells that did not express COX-2. Triptolide also inhibited LPS-stimulated induction of COX-2 mRNA and synthesis of PGE2, at the same inhibitory concentration as seen with the EA extract. The effects of T2, EA, and triptolide paralleled the inhibitory action of dexamethasone. CONCLUSION: The data indicate that both the T2 and EA extracts of TWHF, as well as the triptolide component, inhibit PGE2 production in a variety of human cells by blocking the up-regulation of COX-2.

Acetates↗

PubMed1998

In vivo topical EPR spectroscopy and imaging of nitroxide free radicals and polynitroxyl-albumin.

Piperidine nitroxides have considerable clinical potential, both as antioxidant therapeutic compounds and contrast agents in magnetic resonance imaging. However, their development has thus far been limited by their rapid bioreduction in vivo. Recently, it was reported that polynitroxyl albumin (PNA) can reverse the bioreduction of the reduced 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in the rat heart, enabling the performance of high resolution EPR imaging for prolonged time (Kuppusamy et al., Biochemistry 35, 7051-7057 (1996)). In this report, the efficacy of PNA in maintaining Tempol concentrations in vivo in mice was demonstrated, using L-band (1.25 GHz) EPR spectroscopy and imaging. The EPR signal of intravenous Tempol had a half-life of 1.0+/-0.2 min and became undetectable within 6 min. Subcutaneous Tempol, however, decayed at a slower rate (half-life, 5.0+/-0.5 min) suggesting that Tempol had been bioreduced to the corresponding hydroxylamine form, Tempol-H. Subcutaneously injected PNA restored 20% of the Tempol signal in the vicinity of the PNA deposit. In vivo topical EPR imaging demonstrated that the Tempol signal was restored at the site of PNA injection, but not at locations remote from the PNA injection site. The ability of PNA to maintain Tempol in its paramagnetic state in vivo should enable a wide range of therapeutic and diagnostic applications of piperidinyl nitroxides.

Albumins↗

PubMed1998

Clinical implication of screening p53 gene mutations in head and neck squamous cell carcinomas.

The role of the tumour-suppressor gene p53 in the tumorigenesis of head and neck cancer has been well established, but the clinical significance of p53 alteration is still unclear. A group of 50 patients with head and neck squamous cell carcinoma (HNSCC) were investigated for p53 alterations. DNA was extracted from fresh tumour samples and polymerase chain reaction/single-strand conformation polymorphism analysis was used to detect p53 gene mutations in the region from exon 5 to exon 9. In addition, p53 protein overexpression was assessed by immunohistochemistry using the monoclonal antibody DO-7 on paraffin-embedded tissue sections. p53 gene mutations were found in 45% and p53 protein expression was detected in 61.2% of tumour samples. While p53 protein expression was not correlated with any clinical factors, p53 gene mutations indicated local regional recurrences of HNSCC. The risk of locoregional recurrence was significantly greater in patients with a p53 gene mutation than in patients with the wild-type p53 gene (P = 0.001). Multivariate analysis confirmed p53 gene mutation to be an independently predictive factor for the tumour recurrence (P = 0.0064). When we analysed p53 gene mutation in 12 patients with primary and recurrent tumours, we found that 4 patients (33.3%) had a different p53 gene mutation in the recurrent tumour from that in the original primary tumour. The results indicate that p53 gene mutations and not protein overexpression are valuable predictors for tumour recurrences and for differential diagnosis of a second primary HNSCC.

Biomarkers, Tumor↗

PubMed1998

Cross-talk between signaling pathways in murine embryonic palate cells: effect of TGF beta and cAMP on EGF-induced DNA synthesis.

Signaling pathways utilized by EGF, cAMP, and TGF beta have been demonstrated to play critical roles in normal palate development. Stimulation of these pathways has been shown in palate cells and numerous other systems to affect cell growth. Because proper regulation of cell growth is critical to palate development, we speculate that fine regulation of palatal cell growth may be accomplished through crosstalk between these signaling pathways. We therefore set out to determine the effects of cAMP and TGF beta on EGF-induced cell proliferation in murine embryonic palate cells. We found that both TGF beta and cAMP inhibited the proliferative response of cells to treatment with EGF, whereas H89, a serine/ threonine protein kinase inhibitor with selectivity towards cAMP-dependent protein kinase, increased the cells' proliferative response to EGF. Genestein, a selective inhibitor of tyrosine kinases, at high doses abrogated the cells' proliferative response to EGF, confirming that EGF's ability to induce cell proliferation is critically dependent upon tyrosine kinase activity. Lower doses of genestein, however, actually enhanced cellular response to EGF. The data suggest that both the TGF beta- and cAMP-mediated signaling pathways may be involved in modulation of the effects of EGF on palate cell growth in vivo.

Animals↗

PubMed1998

Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats.

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.

Acetic Acid↗

PubMed1998

Detoxification of aflatoxin B1 by enzymes isolated from Armillariella tabescens.

Detoxification of aflatoxin B1 (AFB1) by Armillariella tabescens multienzyme, which was isolated from mycelium pellets of A. tabescens, was confirmed by thin-layer chromatography (TLC) and rat assay. The results of toxicology and pathology studies showed that toxicity of AFB1 was minimized after treatment with A. tabescens multienzyme. The result of the Ames test indicated that the mutagenic activity of multienzyme-treated AFB1 was greatly reduced (or inactivated) compared with that of untreated controls. TLC determinations showed that AFB1 at an initial concentration of 16 microM was completely detoxified (100%) by the fungal multienzyme. The infrared spectrum suggests that the multienzyme is responsible for opening the difuran ring of AFB1.

Aflatoxin B1↗

PubMed1998

C-erbB-2 protein expression in oesophageal squamous epithelium from oesophageal squamous cell carcinomas, with special reference to histological grade of carcinoma and pre-invasive lesions.

AIMS: C-erbB-2, an oncogene, is member of the growth factor receptor family. Its role in activation of oesophageal squamous cell carcinoma is poorly understood. The aim of this study was to evaluate the part played by c-erbB-2 in oesophageal squamous cell carcinoma in Hong Kong Chinese patients. METHODS: We examined the expression of the c-erbB-2 oncoprotein in 104 oesophageal squamous cell carcinomas from 89 men and 15 women, ranging in age from 41 to 89 years (mean 63). C-ercB-2 expression was studied with monoclonal antibody, using an antigen retrieval method. RESULTS: Focal c-erbB-2 membrane staining was present in 10 (10%) of 104 squamous cell carcinomas. Staining was also noted in the adjacent dysplastic epithelium (n=2) and non-tumour inflamed epithelium (n=2). In carcinomas, the c-erbB-2 membrane staining was identified only in superficial well-differentiated tumour cells and the expression did not predict biological behaviour. CONCLUSIONS: We conclude that the c-erbB-2 oncoprotein is expressed in a portion of oesophageal squamous cell carcinomas and precursor lesions. This suggests that c-erbB-2 activation plays a certain role, mostly probably during the early stages, in carcinogenesis in oesophageal squamous cell carcinomas from Hong Kong Chinese patients.

Adult↗

PubMed1998

The correlation of the weakening effect on gastric mucosal integrity by 5-HT with neutrophil activation.

The effects of 5-hydroxytryptamine (5-HT) on ethanol-induced gastric mucosal damage and on epithelial and vascular integrity were investigated. Male Sprague-Dawley rats were administered with 5-HT (5 or 10 mg/kg, IP) 30 min prior to the challenge with ethanol (40% v/v, 10 ml/kg, PO). 5-HT dose dependently aggravated ethanol-induced injury in the gastric mucosa. Both xanthine oxidase (XO) and myeloperoxidase (MPO) activities in the mucosa were significantly increased with the high dose of 5-HT, which also potentiated the elevation of these enzyme activities by ethanol. However, the mucosal superoxide dismutase activity was left unaltered. In neutropenic (antineutrophil serum-treated) animals, the ethanol-induced gastric mucosal injury was significantly ameliorated, with or without the pretreatment of 5-HT (10 mg/kg). In addition, the effect of 5-HT on the activity of MPO, but not of XO, was also attenuated in these animals. In the ex vivo gastric chamber study on pentobarbital-anesthetized animals, volume of gastric secretion was significantly decreased in the 5-HT-treated groups, with further reduction after ethanol incubation. Transmucosal potential difference (PD) was significantly reduced in 5-HT-treated rats, which also potentiated the ethanol-induced drop in PD. Nevertheless, 5-HT dose dependently increased mucosal vascular permeability and further enhanced during ethanol incubation. These findings suggest that 5-HT adversely affects the defense mechanisms of the gastric mucosa by reducing the secretory function of the mucosal cells and to weaken the epithelial and vascular integrity. Neutrophil activation appears to be responsible for the detrimental effects of 5-HT partly through the elevation in MPO activity. The increase in mucosal XO activity by 5-HT may induce free radical production and possibly modulate the ulcerogenic processes.

Animals↗

PubMed1998

Involvement of free radicals and histamine in the potentiating action of cigarette smoke exposure on ethanol-induced gastric mucosal damage in rats.

Cigarette smoking has been associated with peptic ulcer diseases. We studied the effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and its relationship with vascular integrity and the possible role of free radicals and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood flow and increased xanthine oxidase (XO) activity but superoxide dismutase (SOD) activity remained unaffected in gastric mucosa. Cigarette smoking followed by ethanol administration significantly potentiated mucosal lesion formation along with augmentation of the mucosal blood flow, vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect of smoking on ethanol-induced gastric mucosal lesion and MPO activity was abolished by pretreatment with allopurinol, terfenadine or ranitidine. Terfenadine and ranitidine also reduced the increased mucosal blood flow and vascular permeability induced by smoking and ethanol combined. These findings suggested that cigarette smoke adversely affected the defense mechanisms of the gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia and increased XO activity. Activation of XO together with histamine H1 and H2 receptors stimulation could lead to neutrophil aggregation and vascular damage. However, the potentiating action of cigarette smoke on ethanol ulceration is unlikely through reduction of SOD activity in gastric mucosa.

Animals↗

PubMed1998

Using static MLC fields to replace partial transmission cerrobend blocks in treatment planning of rectal carcinoma cases.

A treatment planning technique has been developed for using static multileaf collimators to replace partial transmission blocks for treating rectal or cervix carcinoma. The static MLC fields were used to replace the partial transmission block of the anterior-posterior pelvis field for the so-called "thunderbird" technique. Treatment plans were developed and evaluated on a commercial three-dimensional treatment planning system (FOCUS, Computerized, Medical Systems, St. Louis, MO). The result of the treatment plan comparison indicates that the static MLC fields are capable of achieving the same target, inguinal and pelvic dose distribution as the partial transmission cerrobend blocked fields. The MLC fields are easy to modify particularly for the match line adjustments. In conclusion, it is efficient and effective to use static MLC fields to replace partial transmission blocks in the "thunderbird" technique for treating rectal or cervix carcinoma.

Humans↗

PubMed1998

Characterization of the O-linked oligosaccharide structures on P-selectin glycoprotein ligand-1 (PSGL-1).

P-selectin glycoprotein ligand-1, PSGL-1, a specific ligand for P-, E-, and L-selectin, was isolated from in vivo [3H]-glucosamine labeled HL-60 cells by a combination of wheat germ agglutinin and platelet P-selectin- or E-selectin receptor globulin-agarose chromatography. The O-linked oligosaccharides on the ligand were released by mild alkaline sodium borohydride treatment and analyzed by a combination of ion-exchange, size exclusion, lectin, and paper chromatography, together with specific exoglycosidase treatments and chemical modifications. Approximately 91% of the radioactivity released from PSGL-1 was recovered in five O-linked glycans: GalNAc (approximately 4% of the total structures), Galp, 3GalNAc (36%), and Galbeta, 3GalNAc substituted with one (45%), two (6%), or three (3%) N-acetyllactosamine repeat units. None of these structures contained fucose, and the majority were substituted with at least one sialic acid. The N-acetyllactosmine-containing structures appeared to be core 2. The remaining 9% of the radioactivity recovered in O-linked oligosaccharides from PSGL-1, eluted in two peaks at 11.8 and 10.2 glucose units, on size-exclusion chromatography. Results from lectin chromatography and chemical and enzymatic degradation experiments suggest that the major portion of the radioactivity in these peaks is associated with sialylated N-acetyllactosamine-type oligosaccharides, substituted with fucose at the penultimate residue in the nonreducing end. Since both sialic acid and fucose reportedly are crucial requirements for selectin binding, these results suggest that only a minor portion, approximately 4.5%, of the O-linked oligosaccharides on PSGL-1 are involved in the interaction with the selectins.

Carbohydrate Conformation↗

PubMed1998

Ultrasonographic and serologic studies of experimental cysticercosis in rats infected with Taenia taeniaeformis.

Rats experimentally infected with Taenia taeniaeformis were followed-up until 14 weeks post inoculation with eggs (PIE) by hepatic ultrasonographic (US) image and serum antibody response analyses. Parasitic cysts could be imaged as small (2 mm in diameter) anechoic areas with or without a parenthesis-like echogenic small line from two weeks PIE. Immunoblot analysis using antigens from oncospheres (TtO), 30-day-old (TtM-30) and 300-day-old metacestodes (TtM-300) revealed that: (1) these three different developmental stages showed their own unique patterns suggesting the presence of stage-specific antigens; (2) faint IgM antibody responses to some components of TtO and TtM-30 or TtM-300 could be detected from one and two weeks PIE, respectively, and (3) IgG responses to some major components of both TtO and TtM-300, and TtM-30 were easily detected from four and five weeks PIE onwards, respectively. Both TtO and TtM (especially TtM-300) appeared to be highly useful for detection of antibody responses in experimentally infected rats. Due to the easiness in preparation of antigens, fully developed metacestodes may be the best candidate antigens for serodiagnosis. These results strongly suggest that both US image and antibody analyses using antigens from fully developed metacestodes are useful for detection of the early stage of cysticercosis in laboratory animal model.

Animals↗

PubMed1998

Immunoblot analysis of a 10 kDa antigen in cyst fluid of Taenia solium metacestodes.

The diagnostic value of a 10 kDa subunit of 150 kDa protein in cyst fluid (CF) of Taenia solium metacestodes was evaluated. Immunoblot analysis revealed that most sera from patients with neurocysticercosis recognized the 10 kDa subunit strongly (209/217 cases, 84.6%), while a few sera from individuals with other parasitic diseases including alveolar echinococcosis (AE, 2/20, 10%) and cystic echinococcosis (CE, 2/25, 8%) showed faint reactions. Sera of cases with other parasitic diseases, especially AE and CE, exhibited cross reactions against other bands in CF. Both differential immunoblot and immunoprecipitation analyses showed that the 10 kDa subunit was the most specific to cysticercosis and highly antigenic, whereas other components at 20-40, 64, 95 and 106 kDa in CF were cross-reactive. IgG subclass ELISA and immunoblot demonstrated that both IgG4 and IgG1 reactions were predominant in neurocysticercosis and recognized the 10 kDa.

Animals↗

PubMed1998

Nociceptin/orphanin FQ activates mitogen-activated protein kinase in Chinese hamster ovary cells expressing opioid receptor-like receptor.

The effect of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the newly identified opioid receptor-like (ORL1) receptor, on mitogen-activated protein kinase (MAPK) was investigated in Chinese hamster ovary cells stably expressing ORL1 receptor. N/OFQ rapidly stimulated phosphorylation and activity of MAPK (p42 and p44 isoforms) in a concentration-dependent manner. The p42 isoform was preferentially activated by N/OFQ. Maximal activation (5.4 +/- 1.2-fold of basal for p42 isoform) was achieved after a 1-min exposure of cells to 100 nM N/OFQ. The activation was blocked completely by pretreatment with pertussis toxin, but was not reversed by naloxone. U-73122, a phospholipase C-specific inhibitor, significantly inhibited phospholipase C activity, as well as MAPK activation stimulated by N/OFQ. Furthermore, N/OFQ-stimulated MAPK activation was suppressed by a protein kinase C-specific inhibitor, chelerythrine. The results demonstrate that N/OFQ can effectively stimulate MAPK by the activation of ORL1 receptor and pertussis toxin-sensitive G proteins, and that phospholipase C, as well as protein kinase C, is critically involved in these processes.

Animals↗

PubMed1998

Application of a video-optical beam imaging system for quality assurance of medical accelerators.

Method validation techniques were developed and experiments were carried out using a beam imaging system (BIS, Wellhöfer Dosimetrie, Schwarzenbruck, Germany) for routine quality assurance of medical accelerators. The routine quality assurance tasks include x-ray beam flatness and symmetry check, light/radiation field congruence test, beam energy constancy for electrons and mechanical checks for couch and collimator rotations. Comparisons were made between the BIS application and conventional quality assurance methods that use radiographic films or detector arrays. In this work, we have demonstrated efficiency and accuracy of the BIS to perform some of the routine quality assurance tasks for medical linear accelerators.

Electrons↗

PubMed1998

An optimized leaf-setting algorithm for beam intensity modulation using dynamic multileaf collimators.

A leaf-setting algorithm is developed for generating arbitrary beam intensity profiles in discrete levels using dynamic multileaf collimators (DMLCs). The algorithm starts with the algebraic expression for the area under the beam profile. It is shown that the coefficients in this expression can be transformed into the specifications for the leaf-setting sequence. It is proven that the algorithm optimizes beam delivery time and total monitor units for the DMLC leaf setting for intensity modulated radiotherapy (IMRT). The algorithm is demonstrated to be applicable to both the 'step-and-shoot' and 'dynamic' type of beam delivery. The graphical interpretation and numerical implementation scheme of the algorithm is illustrated using a simplified example.

Algorithms↗

PubMed1998

Effects of cigarette smoking on gastric ulcer formation and healing: possible mechanisms of action.

Epidemiologic studies have shown that cigarette smoking is closely related to peptic ulcer disease. The mechanisms by which cigarette smoking adversely affects gastric mucosa have been suggested and elucidated. This article reviews some of the mechanisms involved in cigarette smoking-related gastric ulceration and healing. Experimental findings suggest that cigarette smoking increases xanthine oxidase activity, leukotrienes, and nitric oxide production and also neutrophil infiltration in the gastric mucosa. On the other hand, it reduces blood flow, prostaglandin production, epithelial cell proliferation, and formation of blood vessels in the tissue. These actions are important for ulcer formation and healing. The evidence thus far available strengthens the hypothesis that cigarette smoke is indeed harmful to gastric mucosa through defined mechanisms.

Humans↗

PubMed1998

N-Methyl-D-aspartate attenuates opioid receptor-mediated G protein activation and this process involves protein kinase C.

The effects of N-methyl-D-aspartate (NMDA) on opioid receptor-mediated G protein activation were explored in neuroblastoma X glioma hybrid (NG108-15) cells. Treatment of the cells with NMDA resulted in a remarkable attenuation of [35S]guanosine-5'-O-(3-thio)triphosphate binding stimulated by [D-Pen2,D-Pen5]-enkephalin (DPDPE), a delta-opioid receptor agonist. The effects of NMDA were dose and time dependent with an IC50 value of 5 nM and could be blocked by NMDA receptor antagonists. After NMDA treatment, the DPDPE dose-response curve shifted to the right (EC50 value increased approximately 7-fold, from 6 to 40 nM), and the maximal response induced by DPDPE was reduced by approximately 60%. The effects of NMDA were reversible, and the DPDPE response could recover within 60 min. The functional responses of delta-, mu-, and kappa-opioid receptors in primarily cultured neurons also were attenuated significantly by NMDA treatment. The inhibitory effects of NMDA on opioid receptor-mediated G protein activation could be blocked by coadministration of the protein kinase C (PKC) inhibitors or by elimination of the extracellular Ca2+. Correspondingly, NMDA treatment of NG108 cells significantly elevated cellular PKC activity and stimulated Gialpha2 phosphorylation. Transient transfection into NG108-15 cells of the wild-type Gialpha2 and a mutated Gialpha2 (Ser144Ala) resulted in a 2-fold increase in DPDPE-stimulated G protein activation. The DPDPE responses were greatly inhibited by NMDA treatment in the wild-type Gialpha2-transfected cells but much less affected in the mutant Gialpha2-transfected cells. In summary, NMDA attenuates opioid receptor/G protein coupling, and this process requires activation of PKC.

Animals↗