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Biomedical subjects

S Wei

Publications and source records attributed to S Wei.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Effects of homoharringtonine on proliferation of human retro-ocular fibroblasts].

This is a study amied at the effects of homoharringtonine on the proliferation of human retro-ocular fibroblasts. The human retroocular fibroblasts (HROFb) were cultured and MTT colorimetry assay was used to determine the proliferation of HROFb. The influence of homoharringtonine on the proliferation of HROFb was observed in vitro. The results showed that MTT colorimetry assay could precisely reflect the proliferation of HROFb. The absorbance was directly proportional to the number of the cells (r = 0.996, P < 0.001). The proliferation of HROFb was inhibited by the homoharringtonine and the cell proliferation percentage was correlated positively to the homoharringtonine level (r = 0.6932, P < 0.001).

Cell Division↗
PubMed2000

[Informatics of dental medicine].

Dental informatics is a newly developed discinpline which is integrated by modern stomatology, computer sciences and informatics. In this paper, the concept, importance, basic principle and contents were discussed in details. The relationship among dental informatics and related sciences, the formation and history of dental informatics were also described in this paper.

Medical Informatics↗
PubMed1999

Proteolytic enzymes as a limitation for pulmonary absorption of insulin: in vitro and in vivo investigations.

In vitro biodegradation of insulin in lung cytosol and subcellular pellets of normal and diabetic rats was investigated. Rat lung was homogenized and subcellular fractions were isolated by ultracentrifugation. Degradations of [125I]-insulin after incubation with lung cytosol or subcellular pellets was determined using the trichloroacetic acid method. The results show that insulin is highly degraded in cytosol and subcellular pellets. Cytosolic insulin degradation was strongly inhibited by bacitracin or sodium cholate. The degradation of insulin in the lung cytosol from diabetic rats was significantly less than from normal rat. The lung protease activity reached a maximum at pH 7.4. Enzyme inhibitors like bacitracin and sodium cholate noticeably enhanced the relative pharmacological bioavailability of insulin when given intratracheally with insulin to normal rats. Acidic insulin solutions (pH 3.0) had more pronounced hypoglycaemic effects than neutrol solution (pH 7.0). These in vitro and in vivo results suggest that the proteolytic enzymes in the lung limit pulmonary delivery of insulin. The coadministration of protease inhibitors would be a useful approach for improving the pulmonary absorption of insulin.

Absorption↗
PubMed1999

Expression of catalytically active telomerase does not prevent premature senescence caused by overexpression of oncogenic Ha-Ras in normal human fibroblasts.

All normal cells in culture display a limited capacity to divide and eventually undergo an irreversible growth arrest known as replicative cellular senescence. The development of cellular immortality has been implicated as an important factor in the progression of human cancers. Expression of telomerase has been shown to elicit a bypass of senescence and the acquirement of an extended life span. Although oncogenic Ras induces malignant transformation in most immortal cells, it has been shown to cause a senescence-like cell cycle arrest in presenescent human fibroblasts. To test the relationship between the senescence-inducing effect of Ras and the senescence-bypassing activity of telomerase, we used retroviral vector infection to introduce the catalytic subunit of human telomerase into normal human lung fibroblasts. Cell clones displaying in vitro telomerase catalytic activity and life span extension were obtained. However, these cells still became senescent after infection with a retrovirus vector expressing oncogenic Ha-Ras. No differences in premature senescence phenotypes between normal and telomerase-expressing cells were observed. A small number of colonies were recovered after the introduction of Ha-Ras into either normal or telomerase-expressing cells, but in all cases, these clones failed to express the exogenously introduced Ras. We propose that even in the presence of active telomerase, the cellular senescence machinery remains intact and can be activated by appropriate signals. Consequently, interventions aimed at the activation of the latent senescence program may be a fruitful approach in cancer therapy.

Cell Line↗
PubMed1999

Functional association of TGF-beta receptor II with cyclin B.

Utilizing the cytoplasmic tail of Transforming Growth Factor Receptor Type II (TGFbeta RII) as bait in a yeast two hybrid system, we have identified human cyclin B2 as a direct physical partner of TGFbeta RII. Analysis of deletion mutants of glutathione-S-transferase (GST)-cyclin B2 mapped its binding domain for TGFbeta RII to the C-terminal and revealed a negative regulatory region immediately upstream of the cyclin box. Using recombinant proteins, Cdc2 was demonstrated to indirectly interact with TGFbeta RII via cyclin B2. This interaction was reproduced in THP-1 monocytic cells, where TGFbeta treatment markedly enhanced the ability of cyclin B2 and, correspondingly, Cdc2 from TGFbeta-treated THP-1 cells, to bind the GST-TGFbeta RII fusion protein. More importantly, TGFbeta RII co-precipitated with cyclin B2 in TGFbeta-treated THP-1 cells. TGFbeta treatment also caused threonine phosphorylation of Cdc2 in the TGFbeta RII-cyclin B2-Cdc2 complex in THP1 cells, in parallel with down regulation of Cdc2 function as measured by histone H1 kinase activity. Cyclin B1 had the same capacity to bind TGFbeta RII and mediate indirect Cdc2 binding. These results suggest an alternative mechanism that cell cycle arrest in the G1/S phase caused by TGFbeta may, in part, be due to inactivation of cyclin B/Cdc2 kinase, which is needed for entry into the G2/M phase.

Amino Acid Sequence↗
PubMed1999

Mapping and characterization of quantitative trait loci for non-insulin-dependent diabetes mellitus with an improved genetic map in the Otsuka Long-Evans Tokushima fatty rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously reported four quantitative trait loci (QTLs) responsible for NIDDM on Chromosomes (Chrs) 7, 14, 8, and 11 (Nidd1-4/of for Non-insulin-dependent diabetes1-4/oletf) by a whole-genome search in 160 F2 progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. Our present investigation was designed to identify and characterize novel QTLs affecting NIDDM by performing a genome-wide linkage analysis of genes for glucose levels and body weight and analysis for gene-to-gene and gene-to-body-weight interactions on an improved genetic map with a set of 382 informative markers in the 160 F2 progenies. We have identified seven novel QTLs on rat Chrs 1 (Nidd5 and 6/of), 5 (Nidd7/of), 9 (Nidd8/of), 12 (Nidd9/of), 14 (Nidd10/of) and 16 (Nidd11/of) which, together with the Nidd1-4/of, account for a total of approximately 60% and approximately 75% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F2. While the OLETF allele corresponds with increased glucose levels as expected for the novel QTLs except Nidd8 and 9/of, the Nidd8 and 9/of exhibit heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There are epistatic interactions between Nidd1 and 10/of and between Nidd2 and 8/of. Additionally, our results indicated that the Nidd6 and 11/of could also contribute to an increase of body weight, and that the other five QTLs could show no linkage with body weight, but Nidd8,9, and 10/of have an interaction with body weight.

Animals↗
PubMed1999

Identification of novel non-insulin-dependent diabetes mellitus susceptibility loci in the Otsuka Long-Evans Tokushima fatty rat by MQM-mapping method.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type, non-insulin-dependent diabetes mellitus (NIDDM) in humans. We have previously identified 11 quantitative trait loci (QTLs) responsible for NIDDM susceptibility on Chromosomes (Chrs) 1, 5, 7, 8, 9, 11, 12, 14, and 16 (Nidd1-11/of for Non-insulin-dependent diabetes 1-11/oletf) by using the interval mapping method in 160 F(2) progenies obtained by mating the OLETF and the Fischer-344 (F344) rats. MQM-mapping, which was applied for QTL analysis based on multiple-QTL models, is reported to be more powerful than interval mapping, because in the process of mapping one QTL the genetic background, which contains the other QTLs, is controlled. Application of MQM-mapping in the F(2) intercrosses has led to a revelation of three novel QTLs on rat Chrs 5 (Nidd12/of), 7 (Nidd13/of), and 17 (Nidd14/of), in addition to Nidd1-11/of loci. The three QTLs, together with the Nidd1-11/of, account for a total of approximately 70% and approximately 85% of the genetic variance of the fasting and postprandial glucose levels, respectively, in the F(2). While the OLETF allele corresponds with increased glucose levels as expected for Nidd12 and 14/of, the Nidd13/of exhibits heterosis: heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. There is epistatic interaction between Nidd2 and 14/of. Additionally, our results indicated that the novel QTLs could show no linkage with body weight, but Nidd12/of has an interaction with body weight.

Animals↗
PubMed1999

Influence of gene polymorphisms of the renin-angiotensin system on clinical outcome in heart failure among the Chinese.

BACKGROUND: An association between the DD allele of the angiotensin-converting enzyme gene and a poorer outcome in patients with heart failure has been found in whites. The DD allele frequency is lower in Chinese, but the M235T variant of the angiotensinogen gene is more common in Chinese than whites; it is not known to what extent polymorphisms of the renin-angiotensin system affect clinical status or prognosis in Chinese patients with heart failure. METHODS: We assessed the relations among polymorphism of the angiotensin-converting enzyme gene, angiotensinogen M235T (AGT) gene, and angiotensin type I receptor A1166C gene with left ventricular systolic function, left and right ventricular diastolic function, serum angiotensin-converting enzyme, plasma aldosterone and atrial natriuretic peptide levels at presentation, and clinical outcome at 1 year (survival, hospital admissions) in a cohort of Chinese patients with typical systolic heart failure (n = 82). RESULTS: We confirmed the low prevalence of the angiotensin-converting DD and the angiotensin type I receptor CC genotypes, and high prevalence of the AGT TT genotype in Chinese subjects compared with whites. There was no relation between the various gene polymorphisms and survival at 1 year assessed by multiple regression or Cox regression survival analysis. The AC variant of the angiotensin type I receptor gene was associated with morbidity over a 1-year period (hospital admissions) and increased baseline aldosterone levels, but none of the other polymorphisms correlated with systolic or diastolic function, aldosterone or atrial natriuretic peptide levels. By multiple regression for effects on mortality rate, only atrial natriuretic peptide and age were significant. CONCLUSIONS: In Chinese patients with heart failure, polymorphisms of the renin-angiotensin system do not appear to be related to survival or severity, probably because of the different prevalence of these genotypes in the Chinese. Thus this study illustrates that large interethnic differences in the frequencies of genotype polymorphisms of the renin-angiotensin system exist and results from one ethnic group cannot be extrapolated to another.

Aldosterone↗
PubMed1999

Left and right ventricular collagen type I/III ratios and remodeling post-myocardial infarction.

BACKGROUND: Types I and III collagen have different physical properties, and an increase of type I/III ratio can have a deleterious impact on myocardial compliance and left and right ventricular diastolic function. Post-myocardial infarction, these changes in collagen types may be relevant to the remodeling process and the development of heart failure. METHODS AND RESULTS: In the rat coronary ligation heart failure model, we studied the time course of changes in types I and III and total collagen levels over 10 weeks postinfarction. Collagen types were separately quantified in the left (LV) and right ventricles (RV) by computerized morphometry and standard immunohistochemistry techniques, and also by hydroxyproline analysis, and these were correlated with hemodynamic changes. Compared with sham-operated rats, total collagen level increased 2.5- to 2.9-fold and 1.7- to 2.9-fold in the noninfarcted areas (NIAs) of the LV and RV, respectively, over the 10-week period and showed a good relation with changes in hydroxyproline content (r2 = 0.62; P < .0001). In the NIAs of both the LV and RV, type III collagen level showed a transient twofold increase at 2 weeks, which declined to normal at 4 weeks. Type I collagen level increased twofold at 4 weeks in the NIA of the LV and remained elevated at 10 weeks. In the RV, type I collagen level increased 2.7-fold to a peak at 4 weeks and declined gradually to 1.7 times baseline at 10 weeks. The patterns of change in type I collagen level in the RV correlated with the changes in LV end-diastolic pressure (r = 0.73; P < .0001) and RV weight to body weight ratio (r = 0.73; P < .0001). CONCLUSION: There is a relative greater increase of type I collagen level in the NIA and RV postinfarction, and this may lead to left and right ventricular dysfunction. Separate mechanisms might be involved in the induction of the different types of collagen deposition, with type I collagen levels apparently closely correlating with hemodynamic stress.

Analysis of Variance↗
PubMed1999

Identification of possible quantitative trait loci responsible for hyperglycaemia after 70% pancreatectomy using a spontaneously diabetogenic rat.

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model for obese-type non-insulin-dependent diabetes mellitus (NIDDM) in humans. The OLETF rat exhibits sustained hyperglycaemia after partial pancreatectomy, while the normal control rat does not. This difference is thought to be genetically determined and to be caused by impairment of beta-cell regrowth, a possible event involved in the pathogenesis of NIDDM. Our investigation was designed to identify quantitative trait loci (QTL) responsible for post-pancreatectomy hyperglycaemia by performing a genome-wide scan in an F2 intercross obtained by mating the OLETF and Fischer-344 (F344) rats. We have identified three possible QTL on rat chromosomes (Chrs) 3, 14 and 19 that account for a total of approximately 75% of the genetic variance in the F2. For the QTL on Chr 14, the OLETF allele corresponds with increased glucose levels, as expected. Surprisingly, for the QTL on Chr 19, the F344 allele corresponds with increased glucose levels. The Chr 3 QTL exhibits heterosis, heterozygotes showing significantly higher glucose levels than OLETF or F344 homozygotes. We also found evidence for interaction (epistasis) between the QTL on Chrs 14 and 19.

Animals↗
PubMed1999

Radiation-induced changes in nucleotide metabolism of two colon cancer cell lines with different radiosensitivities.

PURPOSE: To investigate changes in nucleotide metabolism after irradiation. MATERIALS AND METHODS: HT29 and SW48 human colon carcinoma cells were exposed to 60Co gamma-rays at doses ranging from 0 to 7.5 Gy. At different times after irradiation, the activities of nine enzymes involved in nucleotide metabolism were measured, the levels of thymidine kinase and deoxycytidine kinase proteins were evaluated by Western blot, and cell-cycle kinetics were analysed by flow cytometry. RESULTS: Changes in enzyme activities concerned not purine but pyrimidine metabolism and essentially the salvage pathway for deoxyribonucleotide synthesis. They were greater in the less radiosensitive HT29 cells. The levels of thymidine kinase and deoxycytidine kinase proteins changed in parallel with their activities. The metabolic changes in irradiated cells did not seem to be due to S-phase transition and the pattern of enzyme activity changes was different from that observed in proliferative cells. CONCLUSIONS: Radiation-induced changes in the salvage pathway for pyrimidine deoxyribonucleotide synthesis were observed. These findings could be exploited in cancer therapy because higher enzyme activities after irradiation suggest that radiation exposure may render cells more sensitive to the drugs activated by these enzymes.

Cell Cycle↗
PubMed1999

A multihit, multistage model of chemical carcinogenesis.

Carcinogenesis involves the accumulation of genetic changes within a single cell. Tumor promotion functions in the initial clonal expansion of an initiated cell but is generally not considered to influence later stages. To investigate whether tumor promotion can influence later stages of carcinogenesis we developed a two-hit 7, 12-dimethylbenz[a]anthracene (D) protocol designed to enrich for keratinocytes that contain at least two D-induced genetic alterations. FVB/N mice were initiated with D and promoted with 12-O-tetradecanoylphorbol-13-acetate (T) or treated with acetone (A) vehicle for 6 weeks. At 7 weeks after the start of promotion, but before visible papilloma development, groups of mice were treated with a second dose of D or A and 1 week later T promotion was resumed. D/T/A/T mice developed 2.8 papillomas/mouse and D/A/D/T mice demonstrated an additive tumor response and developed 5.8 papillomas/mouse. Importantly, D/T/D/T mice developed 12.4 papillomas/mouse, thereby demonstrating a synergistic tumor response compared with D/A/D/T and D/T/A/T mice. D/T/D/T papillomas exhibited increases in suprabasal S phase cells and keratin 13 expression when compared with D/T/A/T papillomas. D/T/D/T mice developed squamous cell carcinomas (SCCs) 10 weeks earlier than D/T/A/T mice and demonstrated a 96% malignancy incidence and 1.71 SCC/mouse compared with D/T/A/T mice, which demonstrated a 28% malignancy incidence and 0.32 SCC/mouse. Greater than 90% of D/T/A/T and D/T/D/T papillomas and SCCs contained mutant Ha-ras, while a normal Ha-ras allele persisted in all cases, indicating that a gene other than the remaining normal allele of Ha-ras was a target gene for the second D hit. These data demonstrate that: (i) promotion between the first and second hits has a profound outcome on carcinogenesis, presumably by increasing the probability that a second hit will occur in a previously initiated cell; (ii) continued promotion after the second hit is required for full expression of malignancy; (iii) the classic initiation-promotion protocol can be extended to a multihit, multistage model.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Purine metabolism in two human melanoma cell lines: relation to proliferation and differentiation.

Purine nucleotide metabolism was studied in two human cutaneous melanoma cell lines IPC182 and IGR221. IPC182 cells do not differentiate, while IGR221 cells differentiate spontaneously at confluency, with intense melanin production. The activities of 11 enzymes involved in the de novo or salvage synthesis or the catabolic pathway of purine nucleotides were measured at different times (from day 3 to day 18), after subculture, during exponential growth and the stationary phase, with or without differentiation. The results demonstrated remarkable differences in the enzyme activity levels and/or the evolution from exponential growth to the stationary phase for each cell line, as well as between the two cell lines. In the non-differentiating IPC182 cells, the activity of enzymes involved in purine nucleotide synthesis decreased when the growth rate slowed down and remained at a low level with a concomitant increase in catabolic activities. In the differentiating IGR221 cells, the activity of enzymes involved in purine nucleotide salvage synthesis increased during the proliferative phase and was maintained at a high level when the cells reached confluency and differentiated; catabolic activities were always lower than in the IPC182 cells. This suggests that extra purine nucleotides, synthesized preferentially by the salvage pathway, could be required for the differentiation of human melanoma cells. Since the two cell lines were cultured in the absence of any differentiation-inducing agents, these results indicate that various metabolic modifications are associated with the natural processes of cell proliferation and differentiation. This research could help to identify some of the enzymes involved in purine metabolism as the targets for the induction of differentiation.

5'-Nucleotidase↗