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Biomedical subjects

S Xue

Publications and source records attributed to S Xue.

65 records · Page 4Linked to original sources

Trends in mortality, morbidity, and risk factor levels for stroke from 1960 through 1990. The Minnesota Heart Survey.

OBJECTIVE: The Minnesota Heart Survey is a population-based study designed to monitor and explain trends in cardiovascular mortality, morbidity, and risk factors. DESIGN: Surveillance time-trends study. METHODS: The following trends were examined among men and women aged 25 to 74 years living in Minneapolis-St Paul, Minn: (1) stroke mortality from 1960 through 1990; (2) risk factors in population-based surveys conducted in 1973 through 1974, 1980 through 1982, and 1985 through 1987; and (3) morbidity in a 50% sample of hospitalized discharges for acute-stroke in 1970, 1980, and 1985. RESULTS: Stroke mortality in Minneapolis-St Paul declined slowly from 1960 through 1972 (average fall, 2.4% per year), dropped sharply from 1972 through 1984 (average fall, 6.5% per year), but exhibited little change thereafter (average fall, 1.5% per year). The average level of cardiovascular disease risk factors fell from 1973-1974 to 1985-1987, with the exception of body mass index. In particular, hypertension diagnosis, treatment, and control levels improved substantially between 1973-1974 and 1980-1982, although there was little improvement after 1980-1982. While discharge rates for hospital-coded acute stroke declined substantially between 1970 and 1985 in both sexes, no clear trend was observed in definite stroke rates as validated using standard clinical criteria. Twenty-eight-day case fatality rates of definite stroke improved significantly from 1970 to 1985. CONCLUSIONS: The substantial decline in stroke mortality of more than 50% from 1960 through 1990 appears to have been attributable to both primary and secondary prevention. These data suggest that the long decline in stroke mortality and morbidity in Minneapolis-St Paul has plateaued, although improved detection of stroke with computed tomography prevents an unequivocal conclusion.

Adult↗

Cardiovascular disease risk factors and glucose tolerance. The Wadena City Health Study.

Cardiovascular risk factors were examined in 453 subjects participating in the Wadena City Health Study, a population-based study to assess the relationship between diabetes and glucose intolerance with age. Each subject was classified as either having non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), or normoglycemia, using WHO criteria. Age- and body-mass-adjusted levels of systolic and diastolic blood pressure were lowest for those with normoglycemia, intermediate for those with IGT, and highest for those with NIDDM. Age- and body-mass-adjusted levels of high-density lipoprotein cholesterol were lowest for those with NIDDM, intermediate for those with IGT, and highest for those with normoglycemia, while triglyceride levels were highest for those with NIDDM, intermediate for those with IGT, and lowest for those with normoglycemia in women but not in men. Low-density lipoprotein cholesterol levels were lowest for those with NIDDM, intermediate for those with IGT, and highest for those with normoglycemia. With the exception of men with IGT, no differences by glycemic strata were observed for plasma total cholesterol. The prevalence of smoking showed no consistent pattern by glycemic status. These findings suggest that individuals with IGT have an atherogenic risk factor pattern that may put them at greater risk for coronary heart disease than those with normoglycemia. Intervention strategies such as diet, exercise, and/or drug therapy should be tested to evaluate whether these are effective in preventing conversion to overt diabetes and normalizing cardiovascular disease risk factors.

Adult↗

The quantitative alteration of 5s rRNA during the development of mammalian erythroid cells and its effect on DNA synthesis in SP2/0 mouse myeloma cells.

Mouse myeloma cells (SP2/0) were incubated with 125I-5s rRNA from rabbit reticulocytes and processed for autoradiography. The results indicated that 5s rRNA could pass into the nuclei of mouse myeloma cells. In a separate experiment, SP2/0 were incubated with cold 5s rRNA, then with 3H-TdR and processed for autoradiography. It was found that in the mouse myeloma cells, DNA synthesis and cell division were obviously suppressed. In another series of experiments, rRNA was extracted from rabbit bone marrow, reticulocytes and erythroid cells and from rat embryonic liver and erythroid cells. The rRNA was analyzed by agarose electrophoresis. It was found that the amount of 5s rRNA in various stages of erythroid development changed along with the denucleating process. Thus it seems likely that 5s rRNA from mammalian erythroid cells could play a role in reversing the malignant phenotype of tumor cells and denucleation of mammalian erythroid cells through inhibiting DNA synthesis.

Animals↗

Histo-electrophoretic analysis of the microheterogeneity and region-specificity of isozymes.

An optimal and practical method for high resolution separation and visualization of soluble and membrane-binding isoenzymes is described. By use of this method, non-specific esterase, lactate dehydrogenase and acid phosphatase from different tissues of mice can be separated into more than 50, 30 and 20 components, respectively. Cholinesterase, glucose-6-phosphate dehydrogenase, acid phosphatase, succinate dehydrogenase, lactate dehydrogenase and non-specific esterase isolated from the lumbar spinal cord of chick embryos at different ages can be separated into about 15, 12, 9, 6, 14 and 20 components, respectively. In addition, an attempt has been made to evaluate quantitatively by densitometry differences in enzyme activity among different regions of the same tissue (e.g. spinal cord). The findings revealed that there are differences in isoenzyme components between the dorsal and ventral regions of the spinal cord. Collectively, the combination of direct tissue isoelectric focusing and fast enzyme visualization reveals a greater number of isoenzyme components than can be demonstrated by other means. This method is an extremely useful procedure for understanding and analyzing the nature and topographic localization of isoenzyme components.

Acid Phosphatase↗

[Establishment of Wg3h-neo cell line with two genetic markers].

Plasmid PSV2-neo DNA containing neo gene (PSV2 neo) was successfully transferred into Wg3h cells, a HGPRT-Chinese hamster fibroblast cell line, by calcium phosphate DNA co-precipitating technique. Cells carrying two selectable markers (AGR and G418R) were thus obtained and passed for more than 40 generations, and designated as Wg3h-neo cell line. The existence of PSV2-neo sequences in the Wg3h-neo genome was confirmed by dot-blot hybridization with PSV2-neo DNA probe. Comparative studies showed that no significant difference in morphology, growth rate or genetic characteristics could be found between the Wg3h and Wg3h-neo cell lines.

Animals↗

Rapid analysis of drug effects on the cell cycle.

Using a flow cytometric technique to analyse DNA content and chromatin structure simultaneously, the following parameters of cell cycle progression were estimated in control and drug-treated L1210 cell cultures: (a) the kinetics of cell exit from the G1 phase; (b) the probability of cell exit from the indeterminate portion of the G1 phase, measured as the half-time of cell residence in that state; (c) the duration of the deterministic portion of G1 phase; (d) the rates of cell transit through selected "windows" in S phase; (e) the rate of cell entrance into mitosis; (f) the mean duration of the cell cycle (Tc). These parameters are obtained in a single stathmokinetic experiment from measurements of individual samples withdrawn at 30 min-1 hr intervals from Vinblasatine-treated cultures. In the same experiment mitotic indices are obtained with high statistical accuracy, and may be used to determine the terminal point of drug action. In addition to cell cycle analysis the method makes it possible to detect drug-induced changes in nuclear chromatin that are manifested by varying sensitivity of DNA in situ to denaturation by acid. Such changes were found to be associated with defective chromatin condensation, altered histone modifications or intercalation of the drugs into DNA. Using this technique the effects of sodium n-butyrate and two new antitumor drugs on L1210 cells were investigated.

Animals↗

Sodium butyrate blocks HeLa cells preferentially in early G1 phase of the cell cycle.

The effects of sodium butyrate on the cell-cycle transverse of HeLa cells was re-examined using the kinetic and the premature chromosome condensation methods of cell-cycle analysis. The results of this study indicate that the sodium butyrate effects are dose-dependent and cell-cycle phase-specific. Cells in the early G1 period are the most sensitive to the inhibitory effects of the drug. When HeLa cells in exponential growth were exposed to a 5 mM concentration of butyrate for 48 h. 67% of the cell population was preferentially arrested in the early G1 period as indicated by the condensed morphology of the prematurely condensed chromosomes (PCC). There was no accumulation of cells in the G2 period. The results of this study suggest that hyperacetylation of histones induced by sodium butyrate does not necessarily result in decondensation of chromatin and the butyrate-enhanced protein, which has been reported to be present in butyrate-treated cells, may have a role in the regulation of the transition of cells from early G1 to the subsequent phases of the cells cycle.

Butyrates↗

WT1-targeted immunotherapy of leukaemia.

Since malignant cells are derived from normal cells, many tumour-associated antigens are also expressed in normal tissues. For examples, WT1 is expressed at elevated levels in most leukaemias, but it is also expressed at reduced levels in normal CD34+ haematopoietic stem cells and in progenitor cells of other tissues. Antigen expression in normal tissues is likely to trigger immunological tolerance and thus blunt T cell responses. This could explain the observation that WT1 vaccination in mice frequently fails to stimulate high avidity cytotoxic T cell responses. In order to circumvent tolerance, we have isolated from HLA-A2-negative donors high avidity CTL specific for HLA-A2-presented peptide epitopes of WT1. These allorestricted CTL efficiently kill HLA-A2-positive leukaemia cells but not normal CD34+ haematopoietic stem cells. However, adoptive cellular therapy with allorestricted CTL could only be performed in leukaemia patients rendered tolerant to the infused CTL by prior allogeneic stem cell transplantation. In order to circumvent this limitation, we propose to exploit the TCR of allorestricted CTL as therapeutic tool. TCR gene transfer can be used to take advantage of the specificity of allorestricted CTL and transfer it to patient CTL, while avoiding the transfer of immunogenic alloantigens from the donor CTL to the patient.

Animals↗

Use of the allogeneic TCR repertoire to enhance anti-tumor immunity.

It is well established that antigen-specific T lymphocytes can inhibit tumor growth in humans and in mice, leading to complete tumor elimination in some cases. However, in many cases T cell immunity is unable to successfully control tumor progression. Since tumors are derived from normal tissues, most antigens are shared with normal tissues, although expression levels are usually elevated in malignant cells. Nevertheless, low-level expression in normal cells can be sufficient to render autologous T cells tolerant and thus unable to mount effective immune responses against tumors. Here, we review how allogeneic T cells can be used to isolate T cells that effectively recognise and kill tumor cells, but not normal cells with low level of antigen expression. The TCR of allogeneic T cells can be introduced into patient T cells to equip them with anti-tumor specificity that may not be present in the autologous T cell repertoire.

Graft vs Host Disease↗