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Biomedical subjects

Y Dong

Publications and source records attributed to Y Dong.

At least 199 records · Page 11Linked to original sources

Serine protease inhibition and mitochondrial dysfunction associated with cisplatin resistance in human tumor cell lines: targets for therapy.

Indicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor-plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride ([Au(DPPE)2]Cl), CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rh123), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-Sla was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.

Adenosine Triphosphate↗

Characterization of human and pig kidney long-chain-acyl-CoA dehydrogenases and their role in beta-oxidation.

Long-chain-acyl-CoA dehydrogenase (LCADH) has been produced by recombinant techniques from the human cDNA and purified after expression in Escherichia coli. Pig kidney LCADH was purified using an optimized method which also produces apparently pure short-chain-acyl-CoA dehydrogenase (SCADH) and medium-chain-acyl-CoA dehydrogenase (MCADH) in good yields. LCADH from both sources has a maximal turnover rate (Vmax of 650-700 min(-1) at pH 7.6) with the best substrates, which is approximately fivefold higher than reported previously. The human enzyme has an approximately fivefold higher Km compared with the pig kidney enzyme with substrates of chain length from C10 to C18 and a significantly different dependence of Vmax on the chain length. Pig kidney LCADH has a similar Vmax/Km with C10 to C14 substrates as MCADH does with C6 to C10 substrates. Recombinant human LCADH, however, is significantly less efficient (approximately fourfold with C12) than purified pig kidney enzyme. We conclude that human LCADH is either quantitatively less important in beta-oxidation than in the pig, or that post-translational modifications, not present in the recombinant human enzyme, are required to optimize human LCADH activity. Our results demonstrate that LCADH is as important as the other acyl-CoA dehydrogenases in fatty acid oxidation at physiological, mitochondrial pH with optimal substrates of chain length C10-C14. The extent of the LCADH-flavin cofactor reduction observed with most substrates and the rate of the subsequent reoxidation with oxygen are markedly different from those found with human medium chain acyl-CoA dehydrogenase. Both LCADH are inactivated by the substrate analogue 2-octynoyl-CoA, possibly via covalent modification of Glu261, the active-site residue involved in deprotonation of the substrate (alpha)C-H.

Acyl-CoA Dehydrogenase↗

The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production.

Rotavirus infection is the leading cause of severe diarrhea in infants and young children worldwide. The rotavirus nonstructural protein NSP4 acts as a viral enterotoxin to induce diarrhea and causes Ca2+-dependent transepithelial Cl- secretion in young mice. The cellular basis of this phenomenon was investigated in an in vitro cell line model for the human intestine. Intracellular calcium concentration ([Ca2+]i) was monitored in fura-2-loaded HT-29 cells using microscope-based fluorescence imaging. NSP4 (1 nM to 5 microM) induced both Ca2+ release from intracellular stores and plasmalemma Ca2+ influx. During NSP4-induced [Ca2+]i mobilization, [Na+]i homeostasis was not disrupted, demonstrating that NSP4 selectively regulated extracellular Ca2+ entry into these cells. The ED50 of the NSP4 effect on peak [Ca2+]i mobilization was 4.6 +/- 0.8 nM. Pretreatment of cells with either 2.3 x 10(-3) units/ml trypsin or 4.4 x 10(-2) units/ml chymotrypsin for 1-10 min abolished the NSP4-induced [Ca2+]i mobilization. Superfusing cells with U-73122, an inhibitor of phospholipase C, ablated the NSP4 response. NSP4 induced a rapid onset and transient stimulation of inositol 1,4,5-trisphosphate (IP3) production in an IP3-specific radioreceptor assay. Taken together, these results suggest that NSP4 mobilizes [Ca2+]i in human intestinal cells through receptor-mediated phospholipase C activation and IP3 production.

Animals↗

Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis.

Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16-positive tumour cells was associated with advanced stage and grade, and with poor prognosis in cancer patients. For FIGO stage I tumours, a high proportion of p16-positive tumour cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to tumour cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival. When all parameters were combined in a multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumour progression. High expression of p16 in the stromal cells of tumours from long-term survivors suggests that tumour growth is limited to some extent by factors associated with p16 expression in the matrix.

Biomarkers, Tumor↗

Expression of MUC1 and MUC2 mucins in epithelial ovarian tumours.

This is the first study to describe the association between expression of MUC1 and MUC2 mucins and prognosis in ovarian cancer. Paraffin sections of epithelial ovarian tumours (n = 182: 29 benign, 21 low malignant potential, and 132 invasive tumours) were analysed immunohistochemically for expression of MUC1 and MUC2 mucin core proteins. Most benign, low malignant potential, and invasive tumours showed high MUC1 expression in the cytoplasm. Low cytoplasmic expression of MUC1 was a predictor for good prognosis, particularly within stage III tumours. A minority of benign epithelial tumours, but most low malignant potential and invasive non-mucinous tumours, showed high MUC1 expression on the cell membrane. High apical MUC1 reactivity was associated with non-mucinous tumours. Low expression of MUC1 in the apical membrane was associated with early stage and good outcome for invasive tumours. Most benign and low malignant potential tumours, but only a minority of invasive tumours, showed MUC2 expression. MUC2 was found in non-mucinous as well as in mucinous tumours. The presence of MUC2 was inversely associated with high tumour grade but was not associated with altered survival. These results support experimental evidence that MUC1 influences the metastatic ability of ovarian cancer.

Adolescent↗

Atrophy of the corpus callosum, cognitive impairment, and cortical hypometabolism in progressive supranuclear palsy.

Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease.

Aged↗

Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumatoid synovial fibroblasts.

OBJECTIVE: To examine the expression of genes of the HOX D cluster in the synovial tissue of patients with rheumatoid arthritis (RA), and to determine whether basic fibroblast growth factor (bFGF) influences the expression and transcriptional regulation of the gene. METHODS: The expression of genes of the HOX D cluster, including HOX4C, HOX4D, HOX4H, and HOX4I, was determined in the synovium of 4 patients with RA and 4 with osteoarthritis (OA) by in situ reverse transcription (RT) and RT-polymerase chain reaction (RT-PCR). The induction of HOX4C messenger RNA (mRNA) by bFGF was determined by RT-PCR. The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay. NIH-3T3 cells transfected with a construct containing C2 binding sequence were incubated with bFGF, and the activity of the reporter was measured by luciferase assay. RESULTS: Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C. HOX4D, HOX4H, and HOX4I genes were expressed in all synovial samples from RA and OA patients. The presence of HOX4C mRNA was also confirmed by RT-PCR and Southern blotting. Treatment with bFGF increased the expression of HOX4C mRNA in RA fibroblasts. The mobility shift assay and luciferase assay showed that bFGF enhanced C2 binding activity and significantly increased the transcriptional activity on RA fibroblasts. CONCLUSION: Our findings suggest that HOX4C is involved in synovial hyperplasia, and that the transcriptional regulation of HOX4C genes by bFGF may play a crucial role in the pathogenesis of RA.

Arthritis, Rheumatoid↗

In vitro inhibition of proliferation of HL-60 cells by tetrandrine and coriolus versicolor peptide derived from Chinese medicinal herbs.

Coriolus versicolor polysaccharide peptide (CVP) and the bis-benzylisoquinoline alkaloids, tetrandrine (TET) and berbamine (BER), the active ingredients isolated from Chinese medicinal herbs known to possess antitumor activities, concentration-dependently inhibited the proliferation of human leukemic HL-60 cells. CVP did not affect the growth of normal human peripheral blood lymphocytes (PBL), whereas TET elicited concentration-dependent cytotoxic effects. Morphological observation and DNA analysis revealed that CVP elicited no effect on the morphological features of HL-60 cells and did not cause DNA fragmentation, but TET and BER caused cell shrinkage with the formation of apoptotic bodies, and showed clear evidence of DNA fragmentation. These findings indicate that TET and BER, but not CVP, inhibited the proliferation of HL-60 cells via induction of apoptosis.

Alkaloids↗

Effects of hormone replacement therapy on serum amyloid P component in postmenopausal women.

The pentraxin serum amyloid P component (SAP) is a 9.5Sz1-glycoprotein and it has recently been found to be deposited in atherosclerotic lesions or neurofibrillary tangles, which are related to the aging process and Alzheimer's disease. The level of SAP was measured by micro single radial-immunodiffusion. Sample sera were obtained from 420 healthy humans, from newborn to 86 years old. The changes in SAP during the menstrual cycle were investigated in 6 women that were 20-21 years. Fifty of the postmenopausal women, suffering from climacteric symptoms, were administered either conjugated estrogen (E), or dehydroepiandrosterone (DHEA). The SAP levels increased with age, being 1.12 +/- 0.82 mg/dl (means +/- S.D.) in neonates, and 6.15 +/- 0.92 mg/dl in persons over 80 years. The SAP level in the females between 15 and 49 years (3.32 +/- 0.95 mg/dl) was significantly (P < 0.001) lower than that in the males in the same age group (5.19 +/- 1.25 mg/dl). The SAP level in the follicular phase was significantly (P < 0.01) lower than that in menstrual phase (menstrual: 4.36 +/- 0.90 mg/dl versus follicular: 2.61 +/- 0.99 mg/dl). In the post-menopausal women that were administered E (1.25 mg/day), the SAP decreased significantly (P < 0.001) from the prelevel of 5.64 +/- 1.40 mg/dl to 4.26 +/- 0.98 mg/dl on the 14th day. In the postmenopausal women that were administered DHEA (60 mg/day), the SAP increased rapidly from the prelevel of 4.97 +/- 0.76 mg/dl to 6.17 +/- 1.20 mg/dl on the 21st day. SAP seems to be a marker that can monitor the effect of hormone replacement therapy.

Adolescent↗

Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan.

A case control design was used to investigate human papillomavirus (HPV) prevalence and risk factors associated with development of cervical squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan. One hundred and twenty-three women with histologically confirmed SIL or CC were compared to a control group of 778 cytologically normal women. With the use of a polymerase chain reaction (PCR)-based method for detection of low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and 58) HPVs, a high prevalence of HPV infection was observed in smokers among the controls. Logistic regression analysis demonstrated that high-risk HPV infection was the most significant risk determinant for LSIL (OR=9.4, 95% CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC (OR=97, 95% CI=35-269). It also showed that unmarried women, women married for 5 to 19 years and smokers represented high risk groups for SIL, while smokers and women with a history of many pregnancies/parities had increased risk for CC. Smoking was the only HPV infection-independent factor for CC, suggesting that smoking may have a carcinogenic effect on the cervix. Since neither history of other cancer nor family cancer history was associated with SIL or CC, genetic factors appear to play little role in cervical carcinogenesis. The risk for cervical neoplasia due to HPV infection increased after marriage in Japan, suggesting a role for husbands as carriers of HPV transmission. Protection from high-risk HPV infection may be of greatest importance for prevention of cervical cancer.

Adolescent↗

Assessment of benzodiazepine receptors using iodine-123-labeled iomazenil single-photon emission computed tomography in patients with ischemic cerebrovascular disease. A comparison with PET study.

BACKGROUND AND PURPOSE: [123I]Iomazenil (IMZ) is a tracer used for single-photon emission computed tomography (SPECT) that has the characteristics of selectively binding to central benzodiazepine receptors (BZR) in the neuron membrane. To determine whether IMZ SPECT provides new information on assessing neuronal damage after ischemic insult to the brain, we compared IMZ SPECT images with the cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and cerebral metabolic rate of glucose (CMRGlc) studied by position emission tomography in the chronic stage of ischemic stroke. METHODS: Five patients (male; mean age, 63.2 +/- 6.0 years) with ischemic cerebrovascular disease and 6 age- and sex-matched normal control subjects were studied. IMZ images obtained 180 minutes after injection were analyzed for BZR binding, and these images were compared with the CBF, CMRO2, and CMRGlc obtained by position emission tomography in the same perfusion areas both visually and quantitatively. RESULTS: In the visual analysis of data obtained from 4 patients with subcortical infarction, decreased IMZ accumulation was observed locally in the overlying normal-appearing cortices of the affected hemisphere, where extensive hypoperfusion and hypometabolism were seen on the images of CBF, CMRO2, and CMRGlc. The regional relative IMZ uptake (regional to cerebellar ratio) for all 5 patients was significantly correlated with the corresponding regional CMRO2 values (r = .45, P < .05). However, no significant correlation was found of the IMZ uptake with either the regional CBF or the regional CMRGlc. CONCLUSIONS: The use of IMZ SPECT provides new information on the neuronal alteration induced by chronic ischemic cerebrovascular disease.

Aged↗

Effect of diaspirin crosslinked hemoglobin on systemic and regional blood circulation in pregnant rats.

Diaspirin crosslinked hemoglobin (DCLHb: Baxter Healthcare Corp., Round Lake, IL, USA) is a biochemically stable hemoglobin based solution with excellent oxygen carrying capacity. Studies have been conducted in male rats to determine the effect of DCLHb on systemic and regional blood circulation. However, the cardiovascular effect of DCLHb has not been studied in female rats. In the present study the effect of DCLHb (400 mg/kg, i.v.) was observed on systemic hemodynamic parameters and regional blood circulation in non-pregnant rats, and in 9-day pregnant and 18-day pregnant rats. DCLHb increased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased blood flow to the heart, gastrointestinal tract (GIT), mesentery & pancreas, and skin in all groups of rats. The basal blood flow to the ovaries was higher in 18-day pregnant rats when compared to non-pregnant and 9-day pregnant rats. DCLHb further increased blood flow to the ovaries of 18-day pregnant rats. It is concluded that DCLHb increases blood flow to the heart, GIT and skin as a result of redistribution of blood from the musculoskeletal system. Blood flow in female reproductive organs is not altered by DCLHb in non-pregnant rats and during mid-term pregnancy. However, in advanced stages of pregnancy DCLHb increases blood flow to the ovaries.

Animals↗

[The immunogenicity of tooth allografts in mice].

The mice used in this study were of the in-bred strains C57BL/6 and Balb/c which differ at the major histocompatibility complex (MHC). The immunogenicity of tooth allografts was studied in vitro by means of detecting the response of Antibody-Complement Mediated Cytotoxity (ACMC) and Cell Mediated Cytotoxity (CMC) of the host. We found that there was significant difference for both ACMC and CMC activity between the allogenic and isogenic tooth transplantation (P < 0.01). The results indicate that tooth allografts are immunogens and do evoke the immune response of recipients.

Animals↗

[Application of serum bile acid chromatography to the diagnoses of liver diseases].

In order to explore the specificity of serum bile acid (SBA) chromatograph in the diagnoses of different kinds of hepatosis, we investigated by means of gas chromatography the changes of serum bile acids in workers who exposed to hexogen or chloroethylene and in patients who suffered from hepatosis such as acute jaundice hepatitis, chronic active hepatitis, cirrhosis and liver cancer. The results revealed different disturbances of SBA occurring in the liver injuries induced by the two kinds of hepatotoxicant. Serum lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) in workers exposed to hexogen and wre significantly different from those of the control group respectively (P < 0.01, P < 0.01, P < 0.05); on the other hand, only serum LCA and DCA went up in workers exposed to chloroethylene (P < 0.0005, P < 0.001). The main changes both concentrated on the secondary bile acids. In acute jaundice hepatitis, chronic active hepatitis, cirrhosis and liver cancer, serum LCA, DCA, CDCA and cholic acids (CA) all went up in different degrees compared with the control group respectively (P < 0.005, P < 0.025, P < 0.005, P < 0.005). But no difference was noted among the 4 kinds of bile acids (P > 0.5), except that between CA and CDCA. These provided the evidence of the diagnosis and identification of clinical hepato-biliary diseases and occupational liver injures.

Cholic Acids↗

[The influence of teeth positions to lower complete denture retention and health of supporting tissues].

Three kinds of three dimension finite element models of edentulous mandibile and the complete denture were established to investigate the influence of artificial teeth positions to denture retention and the supporting tissue. Ten myodynamic and traditional complete dentures were constructed to compare the difference of artificial teeth positions to alveolar ridge. The results indicated: 1. The stress was not obvious different in mandible when teeth were placed over the crest of the ridge or moved lingually or buccally to the ridge in 3 mm; 2. Under occlusion force, it was beneficial for the lower supporting tissue with artificial molars being placed over the slope of mandible and beneficial for denture retention with molars teeth being placed on the crest of ridge buccally; 3. With the effects of oral muscles, the teeth on the crest of ridge buccally or lingually in 3 mm in molar and premolar regions were respectively available; 4. There were obvious difference in arch width of artificial teeth arrangement between traditional and myodynamic complete dentures, the arch was wider in myodynamic complete denture than that of traditional complete denture at molar region.

Denture Retention↗

[The study and primary application of multimedia teaching and learning system for diseases of temporomandibular joint].

A multimedia computer-assistant teaching and learning system for diseases of temporomandibular joint was reported in this paper. It was designed and implemented in Windows (Chinese) on PC 486. It was emphasized that interactive teaching and learning was an available, funny method and student was the focus of teaching and learning in this system. A satisfied result was obtained by utilizing of this multimedia teaching and learning system for primary application.

Computer-Assisted Instruction↗

[Effects of n-butanol extract from Cortex Ilicis rotundae on blood pressure and heart rate in rate].

It was studied that effects of n-butanol extract from Cortex Ilicis Rotundae on blood pressure and heart rate in differedt state. Results showed that the drug elicited a sgnificant depressor effect on both normal pressure and artery pressure to rise for common carotid artery blocked in rats. Of the two latter decline of percent of blood presure and active time and slowing heart rate were more significan than the former. It was same depressor effect that injected the drug into duodenum but not act to hypotensive rats. These results suggested that the drug induce significantly depressor effect and slow heart rat with the exception of hypotension.

1-Butanol↗