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M L Kuo

Publications and source records attributed to M L Kuo.

88 records · Page 5Linked to original sources
PubMed1994

Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro.

To understand the role of betel quid (BQ) in the pathogenesis of oral submucous fibrosis (OSF) and oral cancer, we used DNA damage, cytotoxicity, and cell proliferation assays to study the pathobiological effects of aqueous extracts of three BQ constituents [betel nut (Areca catechu, BN), inflorescence of Piper betle (IPB), and lime], one BN alkaloid (arecoline), and one BN polyphenol [(+)-catechin] on cultured oral mucosal fibroblasts. Extracts of BN and IPB induced DNA strand break formation in a dose-dependent manner. Extracts of BN and IPB, (+)-catechin, and arecoline decreased cell survival and proliferation in a dose-dependent manner. However, aqueous extract of lime (50-800 micrograms/mL) increased cell proliferation by 20-40%. These results indicate that BQ contains not only genotoxic and cytotoxic agents, but also compounds which stimulate cell proliferation. These compounds may act synergistically in the pathogenesis of OSF and oral cancer in BQ chewers. In addition, five anti-oxidants [glutathione (GSH), cysteine, mannitol, catalase, and superoxide dismutase (SOD)] were tested for their protective effects against the cytotoxicity of BQ constituents. GSH (1.95 and 2.6 mmol/L) and cysteine (4 and 8 mmol/L) prevented the arecoline-induced cytotoxicity. In contrast, mannitol, catalase, and SOD did not decrease the arecoline-induced cytotoxicity. These results indicate that thiol depletion, but not the attack of oxygen free radicals, could be the mechanism for arecoline cytotoxicity. GSH could also protect cells from the cytotoxicity of IPB extract. Increasing dietary intake of GSH-rich foods or dietary supplements of GSH may have chemopreventive potential to reduce BQ-associated oral lesions.

Antimutagenic Agents↗
PubMed1993

Effects of signalling transduction modulators on the transformed phenotypes in v-H-ras-transformed NIH 3T3 cells.

Several signalling transduction modulators were used to examine their effects on the morphological changes, foci formation in soft agar and cellular growth in v-H-ras-transformed NIH 3T3 cells. The results from this study showed that specific tyrosine kinase inhibitors (genistein and tyrphostin 23) and cyclic AMP-elevating agents (forskolin and 3-isobutyl-1-methyl-xanthine) could effectively induce differential flat phenotype of v-H-ras transformant at micromolar concentrations. At the same dose range, both signalling modulators also caused a significant suppression of anchorage-independent and cellular growth in the same transformant. By contrast, compound inhibitors such as protein kinase C (staurosporin and H-7), phospholipase A2 (aristolochic acid), phospholipase C (neomycin sulfate) and cyclooxygenase (indomethacin) all did not alter the cellular morphology or foci formation in soft agar, although PKC inhibitors exhibited a slight inhibition on the cellular growth. Based on these observations, we propose that the alterations of protein kinase A or tyrosine kinase-associated signal pathways is necessary and the original cause of the transformation event, but that increase of the activities of protein kinase C, phospholipase C, phospholipase A2 or cyclooxygenase probably is an indirect result of the v-H-ras-mediated transformation.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Effects of tannic acid on 12-O-tetradecanoylphorbol-13-acetate-induced protein kinase C activation in NIH 3T3 cells.

Tannic acid (TA) is a naturally occurring phenol, which has been found to display an antipromotion effect on mouse skin carcinogenesis. In order to explore the molecular mechanism, we have examined the process of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein kinase C (PKC) activation, including phorbol ester binding, enzyme translocation, autophosphorylation and substrate phosphorylation, and finally the TPA-stimulated DNA synthesis. In an initial study, we found that TA slightly inhibited [3H]phorbol dibutyrate (PDBu) binding to intact cells, and only 30% reduction of phorbol ester binding was observed at the highest dose of TA (100 microM). Further analysis by Scatchard plot showed that TA reduced the Bmax of [3H]PDBu from 1.3 pmol/10(6) cells to 1.1 pmol/10(6) cells, but the Kd was increased from 24 to 30 nM. Analysis by western blot indicated that TA did not interfere with the TPA-induced PKC translocation, whereas TA effectively blocked the TPA-evoked phosphorylation of the membrane-bound PKC moiety and its 80 kDa substrate in a dose-dependent manner. We also found that pre- or post-treatment with TA both lead to a similar reduction of 80 kDa protein phosphorylation and that the TPA-stimulated DNA synthesis was also inhibited by TA in a dose-dependent manner, suggesting that the blockage of protein phosphorylation by TA was of biological significance. In conclusion, the work presented here demonstrated that the antitumor promoting effect of TA was not mediated by competing for the binding site with phorbol ester or interrupting the PKC translocation, but rather by effectively blocking phosphorylation by membrane-bound PKC, possibly through altering the biophysical properties of the membrane environment.

3T3 Cells↗
PubMed1993

Efficient gene transfer into primary murine lymphocytes obviating the need for drug selection.

The efficient introduction of exogenous genes into primary lymphocytes is potentially important both for somatic cell gene therapy and for studying lymphocyte biology. We describe the use of retroviral vectors to efficiently introduce exogenous genes into primary, mature murine lymph node T and B cells, and primary, immature murine CD4- CD8- double-negative (DN) thymocytes. Efficient infection of primary cells was achieved by cocultivation of target cells with lethally irradiated helper cells that produce high titers of retroviral vectors containing either the neomycin phosphotransferase II (neo) gene, or both the neo and the human adenosine deaminase (ADA) genes, in the presence of lymphokines and/or mitogens. Two days postinfection, without neomycin selection, one to five copies of the exogenous genes per cell were detected by Southern blot analysis. Expression of the exogenous human ADA protein was detected at levels comparable to the endogenous murine ADA protein in the mature T and B lymphocytes, and was somewhat lower for the immature DN thymocytes.

Adenosine Deaminase↗
PubMed1993

The genotoxicity of the waste water discharged from paraquat manufacturing and its pyridyl components.

The genotoxic potencies of waste water condensate from paraquat manufacturing and its pyridyl components on V79 cells were evaluated using the alkaline elution assay and 6-thioguanine resistance mutation assay. Although 2,2'-dipyridyl and 2,2',2"-tripyridyl both were highly cytotoxic to the cells, only 2,2'-dipyridyl induced moderate DNA-cleaving activity and a low frequency of thioguanine resistance mutation in V79 cells. However, equally toxic doses of waste water condensate exhibited highly DNA-damaging and mutagenic activities in the same cell system. After chelation of ferrous ions, the number of DNA lesions and frequency of 6-TGr mutations induced by waste water condensate were slightly suppressed, whereas by contrast those induced by 2,2'-dipyridyl were significantly potentiated. These results indicate that the coordination compound formation of pyridyl derivatives of waste water with metal ions, especially ferrous ions, in biological systems may be closely related to these genotoxic mechanisms. Finally, it was found that DMSO (a scavenger of hydroxyl radical) and catalase could remarkably protect cells from genotoxic damage induced by waste water condensate, 2,2'-dipyridyl and their ferrous complexes, but this protection was not observed in cells which were treated with SOD (superoxide dismutase). This suggests that the generation of some unknown active oxygen species may be involved in the genotoxic mechanisms of waste water condensate and its constituent 2,2'-dipyridyl.

2,2'-Dipyridyl↗
PubMed1993

Etiologic diagnosis of pulmonary infection by ultrasonically guided percutaneous lung aspiration.

Ultrasonically (US) guided percutaneous lung aspiration was performed for patients clinically diagnosed as having pneumonia (n = 18) or lung abscess (n = 16) and thus taking antibiotics. The procedure was done because of either unsatisfactory clinical or roentgenographic responses, critical underlying disease or poor general condition in the patients. Most cases with pneumonia showed hypoechoic lesion with irregular margin and typical consolidated change, while some cases showed central necrosis. Microorganisms were identified by stains in 9 cases. The overall sensitivity of needle aspiration and culture was 72.2% (13/18). Five cases failed to grow microorganism in culture, mostly due to delayed resolved pneumonia. In cases with lung abscess, the typical ultrasonographic finding was hypoechoic lesion with irregular margin associated with central necrosis or air-fluid level. The overall sensitivity for needle aspiration and culture was 81.2% (13/16). Only one case of pneumothorax was seen, which was recovered with chest intubation and oxygen inhalation. Our result showed that US-guided percutaneous lung aspiration is a technique with high diagnostic yield and low complication rate for cases with pneumonia or lung abscess.

Adult↗
PubMed1993

[Pulmonary cryptococcosis: analyses of 17 cases in VGH-Taipei].

Seventeen patients with pulmonary cryptococcosis collected at VGH-Taipei from 1967 to 1991 were analysed. Their ages ranged from 16 to 70 years with a mean of 45.2. Twelve were men and five were female. The chief characteristic symptoms and signs were cough (58.8%), fever (29.4%) and dyspnea (23.5%). Nearly one third of cases were asymptomatic and presented with abnormal chest roentgenogram. The chest roentgenogram included single nodule or mass (41.2%), multiple nodules (35.3%), pneumonic patch or consolidation (23.5%). In addition, 5 cases (29.4%) and 4 cases (23.5%) were combined with cavitary formation and pleural effusion respectively. Only two cases had associated immunologic deficiency. No patient was found to have history of breeding pigeon. Five cases didn't receive any treatment but were followed from 6 months to 5 years. The remaining 12 cases underwent medical treatment, surgical resection or a combination of both. Prognosis was good in all except one patient who died of multiple myeloma.

Adolescent↗
PubMed1992

Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid, ellagic acid and indole-3-carbinol in the Salmonella and CHO systems.

Four naturally occurring compounds, indole-3-carbinol (I3C), apigenin (Api), ellagic acid (EA) and tannic acid (TA), were tested for their inhibitory effects against 1-nitropyrene- (1-NP) or 1,6-dinitropyrene (1,6-DNP)-induced genotoxicity in Salmonella tester strains and Chinese hamster ovary (CHO) cells. Api and TA strongly inhibited the bacterial mutagenesis induced by nitropyrenes, while I3C and EA had little or no effect. For example, in TA98, 0.2 mumole Api resulted in 48% and 56% inhibition of the mutagenicity induced by 4 nmole 1-NP and 0.035 nmole 1,6-DNP, respectively. With an equal dose, TA caused 46% and 50% reduction of the mutagenicity induced by 1-NP and 1,6-DNP, respectively. As expected, a good correlation was observed between the antimutagenicity of nitropyrenes and their inhibitory effect on nitroreductase activity. This indicated that one of the possible antimutagenic mechanisms of Api or TA was to inactivate the metabolism of nitropyrenes. Two biological end-points, cytotoxicity and sister-chromatid exchange (SCEs), were used to screen the antigenotoxic effects of these compounds in CHO cells. At the sub-cytotoxic dose, I3C, Api and TA all protected against the cytotoxicity induced by 1-NP and 1,6-DNP, but only TA and Api gave a significant reduction of the frequency of SCEs. Moreover, this reduction was found to be highly dose-dependent.

Animals↗
PubMed1992

[Neurogenic pulmonary edema following a grand mal seizure: a case report].

A case of neurogenic pulmonary edema following a grand mal epileptic seizure is presented. This condition is rather rare and the exact pathophysiology remains unknown, but it is believed that the event may be related to transitional increase of intracranial pressure during seizure attack. Pulmonary edema may be a serious complication of epileptic seizure. Rapid recognition and management is very important since the prognosis depends on the severity of pulmonary edema and appropriate treatment.

Adolescent↗
PubMed1992

Ultrasonically guided needle aspiration biopsy in the diagnosis of advanced superior vena cava syndrome.

From July 1990, 11 cases with advanced superior vena cava (SVC) syndrome were undergone ultrasonically guided needle aspiration or biopsy. Ten cases were diagnosed by thin-needle aspiration cytology. Two cases with cytologic proven lymphoma and one case without cytologic diagnosis were undergone needle biopsy, and two of them were proven to be lymphoma. The diagnostic rate of aspiration cytology was 91.0% (10/11) and of aspiration biopsy was 66.6% (2/3). The diagnostic rate of combination of aspiration cytology and biopsy was 100%. For reducing the incidence of pneumothorax, we strongly recommend this two-stage procedure that needle biopsy was performed only when cytologic diagnosis was not conclusive. Only one case developed pneumothorax in performing needle biopsy. In conclusion, ultrasonically guided needle aspiration biopsy is a safe, convenient, and high-yield diagnostic procedure for selected cases of advanced SVC syndrome.

Adult↗
PubMed1991

[Bronchopulmonary sequestration and pseudosequestration].

Bronchopulmonary sequestration is a rare congenital anomaly in which part of the pulmonary tissue is detached from the normal lung without normal connection with tracheobronchial trees and pulmonary artery. It is supplied by anomalous systemic artery. Pseudosequestration is referred as the combination of systemic arterial supply to lung with normal bronchial connection and coexistent infection. It is presumed that chronically inflamed lung may activate neovascularization from systemic circulation in this strage, we reported 15 cases of all pulmonary sequestration and 1 case of pseudosequestration. Most of the cases were young adults with the mean age of 24.6 years old. The intralobar type comprised 86.6% of all cases. In 84.6% of the cases, the aberrant artery originated from the thoracic aorta. Preoperative diagnosis was gained in 47% of cases. In 80% of all cases, the chest mainly characterized with homogeneous mass lesion or cyst(s) with air-fluid level. The distinction between sequestration and pseudosequestration is a diagnostic challenge because the radiologic findings are similar between both conditions. There are clinically significant complications, such as recurrent infections or massive bleeding during operation.

Adolescent↗
PubMed1990

Induction of ouabain-resistance mutation and cycle-dependent transformation of C3H/10T1/2 cells by N-nitroso-2-acetylaminofluorene.

Ouabain-resistance mutation and cell cycle-dependent transformation were studied concurrently in the C3H/10T1/2 cell line treated with N-nitroso-2-acetylaminofluorene (N-NO-AAF) or N-nitroso-N-2-fluorenylacetamide. N-NO-AAF is a new direct-acting mutagen that exhibits a very short half-life (34 min) in complete medium independent of cell number seeded. With 0.1-0.3 mM of N-NO-AAF, cytotoxicity was noted after exposure for 2 h, but another phase of cytotoxicity was observed between 8 and 24 h. N-NO-AAF was more toxic than its parent compound 2-AAF. Moreover, maximal mutation frequency at the Na+/K(+)-ATPase gene locus (ouar mutation) was attained within 30 or 40 min of exposure, dependent on dosage of N-NO-AAF. With 2-AAF, 2-AF and 2-nitrofluorene, however, no detectable mutants were found under the same conditions. In cell cycle-dependent transformation assays, cells were synchronized by release from confluence-induced arrest of proliferation, 2 concentrations of N-NO-AAF were added for 2 h at various intervals during the cell cycle. The results clearly revealed that cells in 2 specific time intervals were susceptible to malignant transformation, i.e., at 10 and 18 h (early S phase) after release from the block.

2-Acetylaminofluorene↗
PubMed1989

The relationship between DNA damage and mutation frequency in mammalian cell lines treated with N-nitroso-N-2-fluorenylacetamide.

The induction of DNA single-strand breaks in C3H10T1/2 mouse fibroblasts and Chinese hamster ovary (CHO) cells by N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA) was demonstrated by the alkaline elution technique. Without metabolic activating system (i.e., rat liver S9 fraction), N-NO-2-FAA exhibits more direct and strong damaging effects on DNA than its parent compound, 2-FAA, at equal concentration in both cell lines. To compare the DNA-damaging potency of N-NO-2-FAA with other well-known carcinogens, such as benzo[a]pyrene, 2-nitrofluorene, and N-methyl-N'-nitrosoguanidine (MNNG), the order of potency is as follows: MNNG (5 microM) greater than N-NO-2-FAA (150 microM) greater than benzo[a]pyrene (20 microM) at equitoxic concentrations, LD37, in the same cell system. Another parallel experiment indicated that N-NO-2-FAA could disrupt the superhelicity of circular plasmid DNA (pBR 322) at a dose range of 0.1-50 mM; however, a complete conversion to form III linear DNA was found at the highest concentration (50 mM). After treatment with various concentrations of N-NO-2-FAA, ouabain resistance (ouar) was induced in C3H10T1/2 cells, while both ouar and 6-thioguanine resistance (6-TGr) were induced in CHO cells. The mutation frequency in the Na+/K+-ATPase locus in CHO cells (1.5 X 10(-6) mutants/microM) is higher than that in C3H10T1/2 cells (1.0 X 10(-6) mutants/microM). The maximal mutation frequency at the Na+/K+-ATPase gene locus was attained with 30 min of exposure in C3H10T1/2 cells, whereas the mutation frequency in CHO cells continued to increase up to 80 min of treatment. Similarly, the maximal mutation frequency at the HPRT locus also continued to increase up to 80 min of treatment. Finally, a linear plot of alkali-labile lesions versus 6-TGr mutations was obtained; but the same relationship was not observed in the case of ouar mutation.

2-Acetylaminofluorene↗
PubMed1988

N-nitroso-N-2-fluorenylacetamide: a new direct-acting mutagen and teratogen.

Reaction of N-2-fluorenylacetamide (2-FAA, CAS No. 53-96-3) with nitrous fume (N2O3) in glacial acetic acid at 0 degree C yields N-nitroso-N-2-fluorenylacetamide (N-NO-2-FAA), 3-nitro-N-2-fluorenylacetamide, N-nitroso-3-nitro-N-2-fluorenylacetamide and other compounds. N-NO-2-FAA is the major product (80%) and fairly stable at low temperature (-20 degrees C), but extremely labile at ambient temperature. The chemical structure of N-NO-2-FAA is characterized by spectrometric analysis of its naphthol coupling derivatives. This new compound is highly mutagenic to Salmonella typhimurium TA97, TA98, TA100 and TA1538 and requires no microsomal metabolic activation. The mutagenicity of N-NO-2-FAA in TA98 is higher than that of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, CAS No. 70-25-7) and N-acetoxy-N-2-fluorenylacetamide (N-AcO-2-FAA). The teratogenic potential of N-NO-2-FAA was studied with white Leghorn chick embryos given a single dose of 1-100 micrograms/egg on day 6 of incubation. A high incidence of flaccid paralysis of the legs and a low incidence of feather, claw and bill malformations were found in the treated group; no such malformed embryos were found in the control group. The teratogenicity of N-NO-2-FAA was found to be weaker than that of MNNG, but comparable to that of N-methyl-N-nitrosourea (CAS No. 684-93-5). N-NO-2-FAA is a strong electrophile and reacts readily with histidine, lysine, cysteine, glutathione, tryptophan, adenosine, cytidine at neutral pH. In contrast to N-AcO-2-FAA, N-NO-2-FAA does not react significantly with guanosine and thymidine. It seems that N-NO-2-FAA is a strong direct-acting mutagen and probably a new prototype of synthetic carcinogen.

2-Acetylaminofluorene↗
PubMedDate not supplied

The interaction of hydroxyurea and ionizing radiation in human cervical carcinoma cells.

PURPOSE: The results from prior in vitro and in vivo studies and recent phase 3 clinical trials suggest a significant potential role for hydroxyurea (HU) as a clinical radiosensitizer for cervix cancer. However, a detailed study of possible cellular mechanisms of radiosensitization in human cervix cancer cells as a consequence of dose and timing of HU and ionizing radiation (IR) has not been performed. This in vitro study analyses the interactions of HU and IR in a human cervical carcinoma cell line, Caski. MATERIALS AND METHODS: Exponentially growing Caski cells were continuously exposed to clinically achievable but minimally cytotoxic concentrations of HU (0.3-3.0 mM) for various time intervals (6, 12, 18, 24, and 30 hours) up to one population doubling time either prior to or immediately following IR (2-8 Gy). The radiation survival data were analyzed using our modification of the linear-quadratic model to test for an interaction (greater than additive). The effects of HU alone, IR alone, and the combination on cell cycle progression and on apoptotic cell death in exponentially growing Caski cells were measured. RESULTS: We report a significant HU-IR interaction (radiosensitization) based on the sequence of HU exposure (post- > pre-IR) and with increasing concentrations of HU (0.3-3.0 mM), but no effect on radiosensitization with the duration of exposure to HU for up to one cell population doubling (6-30 hours). HU concentration has a significant effect on both alpha and beta linear-quadratic values in the post-IR sequences. Exposures of exponentially growing Caski cells to 1 mM and 3 mM HU alone result in a complete block in early S phase throughout the 30-hour exposure, while 0.3 mM HU causes a transient early S-phase block over the initial 12 to 18 hours of exposure. HU alone has no effect on cell cycle progression in G1 or G2/M populations but results in a large apoptotic population (31% following 1 mM HU x 30 hours), which appears to be the principal mechanism of drug cytotoxicity in these cells. IR alone (4 or 6 Gy) results in a significant G2 delay for 6 to 18 hours following IR but no G1 delay and a small apoptotic population at 30 hours post-IR (5.4% vs 2.1% in non-IR controls). The use of HU (0.3 or 1.0 mM) following IR (4 or 6 Gy) results in a significantly larger G2 delay compared with IR alone, but with only an additive effect on the apoptotic population. CONCLUSIONS: These in vitro data demonstrate that radiosensitization of Caski cells is more significant with post-IR exposures to clinically achievable concentrations of HU. This HU-IR interaction is associated with an increased G2 delay, suggesting a reduction in IR damage repair. However, this interaction appears to be independent of the cytotoxicity (principally by apoptosis) from HU alone.

Apoptosis↗