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Biomedical subjects

G Ma

Publications and source records attributed to G Ma.

At least 19 recordsLinked to original sources

Electrocardiographic manifestations: digitalis toxicity.

Toxicity from the digitalis family of cardiac glycoside medications remains common. Successful treatment depends on early recognition; however, the diagnosis of potentially life-threatening toxicity remains difficult because the clinical presentation is often nonspecific and subtle. The hallmark of cardiac toxicity is increased automaticity coupled with concomitant conduction delay. Though no single dysrhythmia is always present, certain aberrations such as frequent premature ventricular beats, bradydysrhythmias, paroxysmal atrial tachycardia with block, junctional tachycardia, and bidirectional ventricular tachycardia are common. Treatment depends on the clinical condition rather than serum drug level. Management varies from temporary withdrawal of the medication to administration of digoxin-specific Fab fragments for life-threatening cardiovascular compromise.

Aged↗

[Polymorphisms of the CYP1A1 and GSTM1 genes and their combined effects on individual susceptibility to lung cancer in a Chinese population].

OBJECTIVE: To investigate the polymorphisms of CYP1A1 and GSTM1 genes as well as their separate and combined effects on individual susceptibility to lung cancer. METHODS: In the matched 106 pairs of patients with lung cancer and non-cancer control persons, genomic DNA were prepared from peripheral blood samples. The genotypes of CYP1A1 Ile/Val and GSTM1+/0 polymorphisms were detected by the allele-specific(AS)-PCR and multidifferential(MD)-PCR. RESULTS: Individuals with genotype Val/Val of CYP1A1, genotype 0/0 of GSTM1, combined genotypes GSTM1 0/0 and CYP1A1 Val/Val, or combined genotypes GSM1 0/0 and CYP1A1 Ile/Val had higher relative risk than those with the corresponding common genotypes and combined genotypes; their odds ratios were 4.02(P=0.03), 1.92(P=0.019), 9.38(P=0.04) and 3.27(P=0.01), respectively. CONCLUSION: There is a synergy of susceptible genotypes GSTM1 0/0 and CYP1A1 Val/Val or CYP1A1 Ile/Val to enhance the individual susceptibility to lung cancer.

Adult↗

Petrochemical exposure and menstrual disturbances.

BACKGROUND: An exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. METHODS: The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 days or less than 21 days, is the major outcome of interest. RESULTS: After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also an important predictor. CONCLUSIONS: This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding.

Adult↗

Amoebic abscess.

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Abdominal Pain↗

High potassium intake inhibits neointima formation in the rat carotid artery balloon injury model.

Recently, we reported that elevated extracellular potassium concentration in vitro inhibited proliferation and migration of vascular smooth muscle cells, formation of free radical compounds by macrophages, and reduced platelet sensitivity to agonists. In the present study we analyzed the effects of long-term, in vivo elevation of extracellular potassium concentration resulting from changes in dietary potassium intake on the vascular response to injury. The rat carotid artery balloon injury model was employed in 70 adult Sprague Dawley rats assigned to three groups. Beginning 14 days before surgical placement of the carotid lesion and continuing until death, the animals were fed diets containing either low (0.1% potassium, n = 25), normal (1.5% potassium, n = 19), or high potassium (4.0% potassium, n = 26). Fourteen days postsurgery the animals were killed and the arteries were analyzed to determine quantitatively the ratio of neointimal to medial area. Dietary potassium had a significant effect on arterial plasma potassium concentration (one-way analysis of variance, P < .01). Group mean and standard errors were 4.26+/-0.12 mmol/L for the low-potassium group, 5.22+/-0.19 mmol/L for normal, and 5.80+/-0.23 mmol/L for the high-intake group. Increases in dietary potassium attenuated neointima formation significantly (P < .05, one-way analysis of variance), with the mean ratio of neointimal area to medial area being 0.447+/-0.106 for the low-intake animals, 0.384+/-.116 for normal, and 0.240+/-.046 for the high-intake group. These results are consistent with a hypothesis that a high level of potassium intake is effective in inhibiting neointima formation in vivo.

Animals↗

Increased potassium concentration inhibits stimulation of vascular smooth muscle proliferation by PDGF-BB and bFGF.

The effects of changes in extracellular potassium concentration on the rate of vascular smooth muscle cell proliferation stimulated by cytokines and serum were analyzed in vitro. To analyze the DNA synthesis response, cells from swine coronary artery were grown in DMEM medium containing 3, 4, 5, or 6 mmol/L potassium together with 20 ng/mL platelet-derived growth factor BB (PDGF-BB), 25 ng/mL basic fibroblast growth factor (bFGF), or 5% fetal bovine serum (FBS), with [methyl 3H] thymidine added, for 24 h. Proliferation responses were analyzed in cells grown in medium with potassium concentrations of 3, 4, 5, or 6 mmol/L, together with either 20 ng/mL PDGF-BB, 25 ng/mL bFGF, or 5% FBS, for 7 days, then harvested and counted. Highly significant inverse relationships were observed between potassium concentration and 3H-thymidine incorporation stimulated by each of the three agonists (P < .01 for each, ANOVA), and between potassium concentration and proliferation (all P < .01, ANOVA). Elevation of potassium concentration within the physiologic range inhibits vascular smooth muscle cell DNA synthesis and proliferation.

Animals↗

Molecular species analysis of 1,2-diacylglycerol released in response to progesterone binding to the amphibian oocyte plasma membrane.

Progesterone, the physiological inducer of amphibian meiosis, acts within minutes at plasma membrane receptors of the Rana pipiens oocyte to release 1,2-diacylglycerol (DAG) from plasma and intracellular membranes. High-performance liquid chromatography (HPLC) analysis of lipid extracts of uninduced oocytes indicates the presence of at least three classes of DAG with a total DAG content of about 150 micromol/kg wet weight. Within 3-5 min after exposure to progesterone, there was a differential increase in all three DAG classes with a twofold increase in total DAG by 10 min. The fatty acid composition of the DAGs in uninduced and progesterone-stimulated oocytes was compared using thin layer chromatographic analysis of lipid extracts from oocytes double-labeled with [14C] or [3H]glycerol and [14C] or [3H]fatty acids. The ratio of labeled fatty acid/labeled glycerol was measured in phosphatidylcholine (PC), phosphatidylinositol (PI) and DAG. The linoleic (18:2) or arachidonic (20:4) acid/glycerol ratios in basal DAG were low compared to that in PC or PI. In contrast, the myristic (14:0), palmitic (16:0) or oleic (18:1) acid/glycerol ratios in basal DAG were relatively high compared to the ratio in PC and PI. A transient increase in both linoleic and palmitic acid labeling of DAG occurred within the first 1-2 min in progesterone-treated oocytes, followed by a return to or below the basal level. Arachidonic and myristic acid labeling of DAG fall within the first minute after progesterone treatment, followed by a sustained rise over the next 10 min. The [3H]oleic acid/[14C]glycerol ratio of DAG does not change significantly following exposure to progesterone. Pretreatment with a phospholipid N-methylation inhibitor (2-methylaminoethane) precluded the rise in linoleic and palmitic acid-rich DAG, whereas pretreatment with a diglyceride kinase inhibitor (D102) produced a sustained elevation of linoleic and palmitic acid-rich DAG. These results indicate that the DAG released in response to progesterone is composed of multiple new molecular species of DAG and that both the palmitate and linolate-rich forms are rapidly phosphorylated to form phosphatidic acid (PA). The newly formed DAG species differ from the basal DAG species and reflect sequential activation of sphingomyelin (SM) synthase, PC-specific phospholipase D (PLD) and PI-specific phospholipase C in response to progesterone, which we have described previously.

Animals↗

Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone.

To develop effective therapies for angiosarcoma, we investigated the anti-tumor effects of etoposide (ETO), TNP-470 and prednisolone (PSL) using an established murine angiosarcoma cell line (ISOS-1). We examined the direct anti-tumor and anti-angiogenic effects of these drugs on ISOS-1 cells and normal murine microvascular endothelial cells (mECs) in vitro. Cell growth of ISOS-1 was inhibited significantly by ETO, moderately by TNP-470, and not at all by PSL (IC(50): 0.25 microg/ml, 10 microg/ml, >8000 microg/ml, respectively). One the other hand, cell growth of mECs was inhibited significantly by TNP-470, slightly by PSL, and negligibly by ETO (IC(50): 0.85 ng/ml, 0.7 microg/ml, 10 microg/ml, respectively). In an in vivo assay, tumor growth of ISOS-1 was significantly inhibited by more than 2.5 mg/kg of ETO dose-dependently, and by more than 30 mg/kg of TNP-470, and 100 mg/kg of PSL individually. Combination treatments of ETO+TNP-470 and TNP-470+PSL showed synergistic enhancement of inhibition (% control inhibition: ETO vs. TNP-470 vs. ETO+TNP-470: 55 versus 55 vs. 16%) (% control inhibition: TNP-470 vs. PSL vs. TNP-470+PSL: 41 vs. 86 vs. 21%). ETO+PSL combination treatment, however, failed to show significant enhancement of anti-tumor effects. In conclusion, our results indicated that TNP-470 may be a very effective drug for angiosarcoma treatment, especially in combination with ETO or PSL. We eagerly anticipate the use of TNP-470 in clinical treatment of angiosarcoma.

Angiogenesis Inhibitors↗

2,2'-Bipyridinium bis(perchlorate)

The title compound, [H(2)bipy](ClO(4))(2) or C(10)H(10)N(2)(2+). 2ClO(4)(-), was obtained at the interface between an organic (2, 2'-bipyridine in methanol) and an aqueous phase (perchloric acid in water). The compound crystallizes in space group P-1 and comprises discrete diprotonated trans-bipyridinium cations, [H(2)bipy](2+), and ClO(4)(-) anions. The cations and anions are connected through N-H.O and C-H.O hydrogen bonds [distances N.O 2.817 (4) and 2.852 (4) A, and C.O 3.225 (6)-3.412 (5)A]. The C-C bond distance between the two rings is 1.452 (5) A. The bipyridinium cation has a trans conformation and the N-C-C-N torsion angle is 152.0 (3) degrees.

Journal Article↗

Inhibition of vascular smooth muscle cell migration by elevation of extracellular potassium concentration.

The effect of potassium on the migration of vascular smooth muscle cells was analyzed in media made with extracellular potassium concentrations of 3, 4, 5, and 6 mmol/L. The migration of cultured porcine coronary artery cells was stimulated with platelet-derived growth factor (PDGF)-BB. In the first study, cells were exposed to PDGF-BB at concentrations of 0, 10, or 20 ng/mL for 5 hours with the use of a Boyden chamber. Cells were quiescent overnight in 0.5% fetal bovine serum in Dulbecco's modified Eagle's medium with an extracellular potassium concentration of 4 mmol/L. With increasing potassium concentration, migration was significantly inhibited (P<0. 02, 2-way ANOVA). In the cells exposed to 10 ng/mL PDGF-BB, migration ranged from 500+/-86% to 294+/-44% (value in wells with 0 ng/mL PDGF-BB and 4 mmol/L potassium concentration=100%) in medium containing 3 to 6 mmol/L extracellular potassium concentration (P<0. 03). Long-term potassium exposure was investigated in cells grown in 5% serum in Dulbecco's modified Eagle's medium with an extracellular potassium concentration of 3, 4, 5, or 6 mmol/L for 3 to 4 weeks. Migration was assessed with 0 or 20 ng/mL PDGF-BB. Migration was significantly inhibited by the elevation of extracellular potassium concentration (P<0.01, 2-way ANOVA). With 20 ng/mL PDGF-BB, the migration rates ranged from 152+/-11% in medium with 3 mmol/L potassium to 69+/-5% in 6 mmol/L potassium (P<0.01). Increases in extracellular potassium concentration within the physiological range significantly and directly inhibit vascular smooth muscle cell migration.

Animals↗

Bcr: a negative regulator of the Bcr-Abl oncoprotein.

Chronic myelogenous leukemia is typically characterized by the presence of the Philadelphia chromosome (Ph) in which 5' portions of the BCR gene are fused to a large portion of the ABL gene. Our studies and those of others indicate that Bcr sequences within the Bcr-Abl oncoprotein are critically involved in activating the Abl tyrosine kinase and actively participate in the oncogenic response, which is generated by the Bcr-Abl oncoprotein. We investigated the role of the Bcr protein in the oncogenic effects of Bcr-Abl. Reduction of the level of the Bcr protein by incubating cells with a 3' BCR anti-sense oligodeoxynucleotide increased the growth rate and survival of hematopoietic cell lines expressing Bcr-Abl. Also, enforced expression of Bcr in Bcr-Abl cell lines strongly reduced transformation efficiency. Induction of Bcr expression drastically reduced the phosphotyrosine content of Bcr-Abl in Rat-1 fibroblasts transformed by P185 BCR-ABL and in hematopoietic cells expressing P210 Bcr-Abl within days following induction of Bcr. Rat-1/P185 cells maintained for three weeks after Bcr induction had dramatically reduced amounts of phosphotyrosine proteins compared to cells in which Bcr expression was repressed by the addition of Tet. In contrast Bcr expression did not decrease the phosphotyrosine content of either v-Src or activated Neu tyrosine kinase. Importantly, the phosphotyrosine content of total P160 BCR (induced plus endogenous) was strongly reduced by inducing expression of Bcr, indicating that the induced Bcr protein was not a target of the tyrosine kinase activity of Bcr-Abl but instead functioned as an inhibitor of Bcr-Abl. These results show that the Bcr protein can function as a negative regulator of Bcr-Abl, but that the inhibitory effects of Bcr are dependent on achieving an elevated level of Bcr expression relative to Bcr-Abl.

Animals↗

Structure-activity relationships: analogues of the dicaffeoylquinic and dicaffeoyltartaric acids as potent inhibitors of human immunodeficiency virus type 1 integrase and replication.

The dicaffeoylquinic acids (DCQAs) and dicaffeoyltartaric acids (DCTAs) are potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase. They also inhibit HIV-1 replication at nontoxic concentrations. Since integrase is an excellent target for anti-HIV therapy, structure-activity relationships were employed to synthesize compounds with: (1) improved potency against HIV-1 integrase, (2) improved anti-HIV effect in tissue culture, and (3) increased selectivity as indicated by low cellular toxicity. Thirty-four analogues of the DCTAs and DCQAs were synthesized and tested for cell toxicity, anti-HIV activity, and inhibition of HIV-1 integrase. Seventeen of the 34 analogues had potent activity against HIV-1 integrase ranging from 0. 07 to >10 microM. Seventeen analogues that were synthesized or purchased had no inhibitory activity against integrase at concentrations of 25 microM. Of the biologically active analogues, 7 of the 17 inhibited HIV replication at nontoxic concentrations. The most potent compounds were D-chicoric acid, meso-chicoric acid, bis(3,4-dihydroxydihydrocinnamoyl)-L-tartaric acid, digalloyl-L-tartaric acid, bis(3,4-dihydroxybenzoyl)-L-tartaric acid, dicaffeoylglyceric acid, and bis(3, 4-dihydroxyphenylacetyl)-L-tartaric acid. Anti-HIV activity of the active compounds in tissue culture ranged from 35 to 0.66 microM. Structure-activity relationships demonstrated that biscatechol moieties were absolutely required for inhibition of integrase, while at least one free carboxyl group was required for anti-HIV activity. These data demonstrate that analogues of the DCTAs and the DCQAs can be synthesized which have improved activity against HIV integrase.

Anti-HIV Agents↗

Promotional effects of CO(2) laser and scalpel incision on 4-NQO-induced premalignant lesions of mouse tongue.

BACKGROUND AND OBJECTIVES: CO(2) laser and scalpel incision have been demonstrated to have promotional effects on oral neoplastic lesions. However, a precise understanding has not been achieved as to which modality has a more significant effect on cancer promotion. The purpose of this study was to determine the histological and biological changes after CO(2) laser surgery and scalpel incision in oral premalignant lesions. STUDY DESIGN/MATERIALS AND METHODS: Premalignant lesions of mouse tongue induced by 4-nitroquinoline-1-oxide (4NQO) in drinking water for 4 months were used in this study. A 2-mm incision was made on the right margin of each mouse tongue, using either a CO(2) laser (group A) or a scalpel (group B). Mice without incisional treatment were used as controls (group C). Seven months after laser and scalpel treatments, hematoxylin-eosin staining and proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR), and p53 immunostaining were performed for tongue specimens. RESULTS: The epithelia of right tongue margins showed more severe dysplasia than those of left tongue margins in both group A and group B. The PCNA labeling indices (LIs) and EGFR expression for right tongue margins were also higher than for left margins in both group A and group B. There was no obvious difference between these two groups. Almost no p53-positive staining was found in either group. CONCLUSION: CO(2) laser surgery and scalpel incision seem to have similar promotional effects on oral premalignant lesions.

4-Nitroquinoline-1-oxide↗

Inverse relationship between potassium intake and coronary artery disease in the cholesterol-fed rabbit.

We tested the hypothesis that a low level of dietary potassium intake would exacerbate the severity of vascular lesion formation in rabbit coronary arteries during high cholesterol intake. Two groups of nine rabbits were studied for 6 weeks while eating a diet containing 2% cholesterol and 0.9% sodium. The normal potassium group consumed a diet containing 1.5% potassium and the low potassium group consumed a diet containing 0.4% potassium. After 6 weeks the animals were killed, the hearts were removed, and blood samples were withdrawn from the abdominal aorta immediately before removing the heart. The hearts were sectioned and slides were prepared and fixed with hematoxylin and eosin. The numbers of normal and abnormal vessels, and those with foam cells in the subintima, were counted in selected sections. Plasma potassium concentration in the normal and low potassium intake groups averaged 4.27 +/- 0.27 mmol/L and 3.90 +/- 0.11 mmol/L, respectively. No differences between the groups were observed in plasma cholesterol or body weight gain. The percentages of abnormal arteries in the groups were 4.20 +/- 0.35 in the normal intake group and 6.36 +/- 0.50 in the low intake group, 51% greater in the normal intake group (P < .001). These results support the hypothesis that low potassium intake exacerbates the severity of subintimal lesion development in the coronary arteries.

Animals↗

Effect of photodynamic therapy using 5-aminolevulinic acid on 4-nitroquinoline-1-oxide-induced premalignant and malignant lesions of mouse tongue.

A new photosensitizing agent 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has been demonstrated as a useful method for treatment of superficial neoplastic lesions. The aim of this study was to determine the effects of topically and systemically ALA-based PDT in neoplastic lesions of the oral cavity. Premalignant and malignant lesions of mouse tongue induced by 4-nitroquinoline-l-oxide (4NQO) were used in this study. At 1, 2 and 3 h after topical application of ALA or 3 h after systemic administration of ALA (250 or 1000 mg/kg), the lesions were irradiated with Nd: YAG dye laser at 630 nm (200 J/cm2). Both premalignant and early malignant lesions showed complete response to systemically ALA-based PDT. In an invasive nodular malignant lesion, however, only the superficial portion was affected. There was no apparent difference in the PDT effect between 250 and 1000 mg/kg doses of ALA. In contrast, topically ALA-based PDT had virtually no effect on most lesions. It was concluded that systemically ALA-based PDT is a useful method for treating premalignant and early malignant lesions in the oral cavity, while topically ALA-based PDT using this preparation may be unsuitable for treatment of oral lesions.

4-Nitroquinoline-1-oxide↗

Vascular protective effects of potassium.

Potential mechanisms responsible for the cardiovascular protection associated with high levels of dietary potassium were investigated in in vitro and in vivo studies. Elevation of extracellular potassium concentration within the physiological range inhibited free radical formation from macrophages and endothelial cells, inhibited proliferation and thymidine incorporation of vascular smooth muscle cells, and reduced platelet sensitivity to thrombin and other agonists. The effects of potassium on several well-characterized animal models of vascular pathology were also studied. Acute elevation of plasma potassium concentration inhibited thrombus formation in the coronary artery of the dog and the carotid artery of the rabbit. In cholesterol-fed rabbits, 6 weeks of diet containing low potassium content increased by approximately 50% (compared with control rabbits) the number of arteries in the myocardium showing signs of arteriosclerotic lesion formation. And in rats and pigs, 4 weeks of eating high potassium-content diet reduced the severity compared with control animals of neointimal proliferation associated with balloon angioplasty. We propose that high levels of dietary potassium provide cardiovascular protection by inhibiting the function of the cells that are responsible for vascular lesion formation.

Animals↗

Association of petrochemical exposure with spontaneous abortion.

OBJECTIVES: To assess the association between petrochemical exposure and spontaneous abortion, a retrospective epidemiological study in a large petrochemical complex in Beijing, China was conducted. METHODS: Plant employment records identified 3105 women who were married, were 20-44 years of age, and had never smoked. Of those, 3070 women (98.8%) reported at least one pregnancy. From this group, 2853 (93%) of the women participated in the study. According to their plant employment record, about 57% of these women workers reported occupational exposure to petrochemicals during the first trimester of their pregnancy. Trained interviewers administered a standardised questionnaire to this group of women and their husbands, collecting information on reproductive history, pregnancy outcomes, employment history, occupational exposure, smoking habits, alcohol consumption, indoor air pollution, and demographic variables. The results from the womens' first pregnancies were analysed. RESULTS: There was a significantly increased risk of spontaneous abortion for women working in all of the production plants with frequent exposure to petrochemicals (8.8%; range of 5.8%-9.8%) compared with those working in nonchemical plants (2.2%; range of 0.0%-7.1%). Also, when a comparison was made between exposed and non-exposed groups within each plant, exposure to petrochemicals was consistently associated with an increased risk of spontaneous abortion. The overall odds ratio (OR) was 2.7 (95% confidence interval (95% CI) 1.8 to 3.9) after adjusting for potential confounders. When the analysis was performed with the exposure information obtained from the women' interview responses for (self reported) exposures, the estimated OR for spontaneous abortions was 2.9 (95% CI 2.0 to 4.0). The analysis was repeated by excluding those 452 women who provided inconsistent reports between recalled exposure and work history, and a comparable risk of spontaneous abortion (OR 2.9; 95% CI 2.0 to 4.4) was found. In analyses for exposure to specific chemicals, an increased risk of spontaneous abortion was found with exposure to most chemicals, and the results for benzene (OR 2.5; 95% CI 1.7 to 3.7), gasoline (OR 1.8; 95% CI 1.1 to 2.9), and hydrogen sulphide (OR 2.3; 95% CI 1.2 to 4.4) were significant. CONCLUSION: An increased risk of spontaneous abortion was found associated with the exposure to petrochemicals, including benzene, gasoline, and hydrogen sulphide.

Abortion, Spontaneous↗