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Biomedical subjects

D Xu

Publications and source records attributed to D Xu.

At least 307 records · Page 17Linked to original sources
PubMed1996

Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation.

Multidrug resistance gene (mdrl) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20-25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. the cell fraction with low DNR content had higher (3.8-40 times)mdr1 mRNA levels in 10/10 patients and higher (1.4-26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation. In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.

Adult↗
PubMed1996

Alcohol and glucose metabolism in skeletal muscles in the rat.

Ethanol is known to cause an acute and profound insulin resistance in man and the rat primarily via effects on glucose utilization. This paper examines the nature of these inhibitory effects on whole-body glucose utilization using the euglycaemic hyperinsulinaemic clamp in the conscious unrestrained rat. We confirm that ethanol infusion causes an acute insulin resistance, the rate of glucose infusion required to maintain euglycaemia (GIR) being decreased markedly by ethanol. To ensure that the GIR is a measure of whole-body glucose disposal, glucose turnover and hepatic glycogen levels were measured. These studies showed that ethanol totally suppressed hepatic glucose production. The reduction in GIR is associated with marked decreases in glucose uptake and glycogen synthesis in most skeletal muscles. In oxidative but not in non-oxidative muscles, the activation of glycogen synthase in response to insulin was decreased by ethanol, suggesting that a defect in glycogen synthase activation may be responsible for the decrease in glycogen synthesis. The basis of the inhibitory effects of ethanol on insulin-stimulated glucose metabolism in muscle is unknown, but may involve membrane-associated impairments in insulin signalling and/or the glucose transport system.

Journal Article↗
PubMed1996

Metabolic effects of alcohol on skeletal muscle.

The purpose of this review is to summarize our current understanding of the acute and chronic interactions between alcohol and nutrient metabolism in skeletal muscle. Insulin is well known to play an important regulatory role in nutrient, especially glucose, uptake and utilization in skeletal muscle. Several studies have shown that alcohol can acutely reduce the normal metabolic responses of skeletal muscle to the action of insulin. The most obvious of these is an acute impairment in glucose metabolism associated with alcohol consumption. While the exact mechanism(s) underlying this acute insulin resistance is presently unclear, several possible factors are discussed in this review. In contrast to these short-term effects, the effects of alcohol on skeletal muscle insulin sensitivity in chronic alcohol abusers are not as well established. Chronic alcohol abuse is known to be associated with skeletal myopathies, believed to result from alcohol induced abnormalities in muscle protein synthesis. Finally, the alcohol-mediated impairments of many aspects of skeletal muscle metabolism are discussed in relation to the insulin resistance associated broad spectrum of common lifestyle-related disorders, including non-insulin dependent diabetes mellitus and obesity, the consequences of which may be important to the pathogenesis of alcohol-related diseases.

Journal Article↗
PubMed1996

Acute ethanol-mediated insulin resistance in the rat: the role of ethanol oxidation.

Ethanol causes an acute and profound insulin resistance in humans and in the rat. Recent studies indicate that defects in skeletal muscle glucose uptake and utilization make a major contribution to this insulin resistance. In this study, we used the euglycaemic hyperinsulinaemic clamp to examine the role that hepatic ethanol oxidation via alcohol dehydrogenase (ADH) plays in the acute insulin resistance caused by ethanol in the rat. Treatment with the ADH inhibitor 4-methylpyrazole (4-MP) failed to abolish the insulin resistance as expressed as a decrease in the rate of glucose infusion required to maintain euglycaemia (GIR). A decrease in GIR was also observed in response to tert-butanol, an alcohol that is not a substrate for hepatic ADH. These results indicate that oxidation via ADH is not a prerequisite for the inhibition by ethanol of whole-body glucose utilization. In a separate study, we examined the relationship between blood ethanol concentration and GIR in order to determine the potency of ethanol in causing insulin resistance. These experiments showed that even at low blood concentrations (<2 mM), ethanol caused a profound decrease in GIR, similar in magnitude to that observed at higher blood concentrations (approximately 40 mM)

Journal Article↗
PubMed1996

Nitrite oxidation of myoglobin in perfused myocardium: implications for energy coupling in respiration.

Nitrite oxidation of oxymyoglobin in perfused rat myocardium under nonlimiting oxygen produces a detectable 1H nuclear magnetic resonance metmyoglobin (metMb) signal at -3.9 ppm. When the myocardium is perfused with < 10 mM nitrite, the 1H nuclear magnetic resonance MbO2 gamma CH3 Val E11 signal does not change intensity and the metMb reporter signal at -3.9 ppm is undetectable. However the rate pressure product decreases by 26% from the control level. Phosphocreatine, myocardial oxygen consumption, Pi, ATP, and pH remain constant. With > 10 mM infused nitrite, myoglobin (Mb) oxidation becomes apparent. As the MbO2 gamma CH3 Val E11 signal intensity decreases, the metMb signal intensity at -3.9 ppm increases. At the same time the 31P high-energy phosphate signals, rate pressure product, and lactate formation exhibit significant alterations. Myocardial oxygen consumption, however, remains constant. The data indicate that Mb oxidation does not limit myocardial respiration but does reduce energy production. Pulse-recovery experiments further demonstrate that a transient perfusion with 2 mM infused nitrite depresses the contractile function, which does not recover during reperfusion with oxygenated, nitrite-free buffer. The findings support the view that either Mb mediates energy coupling or nitrite directly uncouples energy production in myocardium. They also reveal a glimpse of the intracellular reductase activity that maintains the Mb in the Fe (II) state.

Animals↗
PubMed1996

Supression of telomerase activity in HL60 cells after treatment with differentiating agents.

The human promyelocytic leukemic HL60 cells are immortal and as such express high levels of telomerase activity. All-trans retinoic acid (ATRA) and 1 alpha, 25 dihydroxyvitamin D3 (VD3) induce differentiation of HL60 cells into CD11b+ mature granulocytes and monocytes, respectively. We studied telomerase activity after differentiation of HL60 cells. A marked inhibition of the enzyme activity was observed in the differentiated CD11b+ cells after 72-120 h treatment with either differentiating agent. In contrast, the VD3-treated CD11b- HL60 cells, which failed to undergo differentiation and human erythroleukemic cell line K562, exposed to ATRA retained high levels of telomerase activity. This finding suggests, that telomerase activity is repressed as a differentiation-associated event in HL60 cells. Our results provide the first evidence that immortal leukemic cells, like normal human cells, have a telomerase repressing mechanism which can be activated by differentiation and thus lead to the suppression of telomerase activity. This in vitro model may be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.

Calcitriol↗
PubMed1996

Spontaneous malignant transformation of fibrous dysplasia.

OBJECTIVE: To evaluate the clinical and radiological findings in diagnosing spontaneous malignant transformation of fibrous dysplasia. METHODS: Fifteen cases of sarcomatous transformation proved by operation and pathological examinations were found in a group of 356 patients with fibrous dysplasia, and their radiological manifestations were retrospectively studied. The 15 cases included 8 osteosarcomas, 5 fibrosarcomas and 2 chondrosarcomas. All the 15 patients were known to have long-standing fibrous dysplasia, but no radiation therapy was ever received. Eleven patients had polyostotic fibrous dysplasia and 4 had monostotic type. RESULTS: Malignant transformation most frequently occurs in the cystic expansive lesion of the long tubular bone. Pains, swelling and late appearance of a bony mass are the main clinical manifestations. The early radiological features of sarcomatous transformation in fibrous dysplasia are moth-eaten or cystic areas of osteolysis located in the involved bone. The cortical destruction and gradual formation of a soft tissue mass that contains tumor-bone are highly suspicious of osteosarcomatous transformation, while ring-like and spotty calcification in the tumor matrix is indicative of chondrosarcoma. Fibrosarcoma usually shows simple osteolytic destruction. CONCLUSIONS: According to the clinical radiological findings, patients of sarcomatous transformation can be detected in the early stage. These radiological findings may be used as a clue for differentiating various kinds of sarcomatous transformation.

Adult↗
PubMed1996

Rapid HLA-DR genotyping by PCR-amplification with sequence-specific primers.

OBJECTIVE: To establish a rapid genotyping for HLA-DR alleles by polymerase chain reaction with sequence-specific primers (PCR-SSP) for clinical application. MATERIAL AND METHODS: The subjects of study included 69 recipients, 43 unrelated donors and 5 cell lines. Genomic DNA was prepared from peripheral blood leukocytes by a salting-out method. Thirty primers were designed according to the HLA-DRB nucleotide sequences, and synthesized on a 391 DNA synthesizer. Twenty separate PCR reactions were performed for each sample. The amplification was accomplished by 34 cycles consisting of denaturation at 94 degrees C for 30 seconds, annealing at 60 degrees C for 50 seconds and extension at 72 degrees C for 40 seconds. The specificity of matching was determined by standard DNAs and Southern hybridization using DIG labeling probes. RESULTS: All 112 samples and 5 cell lines were able to be typed by PCR-SSP. No false positive or false negative typing results were obtained. The reproducibility was 100%. The size of the specific product was in concordance with the size of the designed primers. The overall time for genotyping was 4 hours. The typing results were confirmed by Southern hybridization. CONCLUSIONS: Genotyping for HLA-DR by PCR-SSP is a rapid and accurate matching technique suited for clinical application.

Alleles↗
PubMed1996

[The preliminary study on the hepatitis B virus infection rate of peripheral blood mononuclear cell in both HBsAg and HBeAg-positive pregnant women and its role in intrauterine transmission].

OBJECTIVE: To study the hepatitis B virus (HBV) infection rate of peripheral blood mononuclear cells (PBMC) and the role of infected PBMC in the intrauterine transmission. METHODS: Polymerase chain reaction (PCR) was using for detection of HBV-DNA in PBMC of 52 both HBsAg and HBeAg positive pregnant women just before onset of labour, and HBsAg were detected in sera of their neonates by enzyme linked immunoabsorbent assay (ELISA) within 24 hours after birth. RESULTS: HBV infection rate of PBMC in these women was 46.2% (24/52). There was positive correlation between infection rate of PBMC and HBsAg titre of pregnant women (chi 2 = 4.59, P < 0.05), but no relationship between PBMC infection rate and neonatal HBV infection. CONCLUSION: The possibility of intrauterine transmission of HBV by infected PBMC through transplacental passage was small.

DNA, Viral↗
PubMed1996

[Effects of ginkgo plus on hypoxic pulmonary hypertension in rats].

We examined the effects of Ginkgo Plus on the pulmonary hemodynamics and right ventricular hypertrophy in rats exposed to isobaric chronic hypoxia. The rats treated with chronic hypoxia developed pulmonary hypertension and right ventricular hypertrophy. Ginkgo Plus reduced significantly the hypoxia-induced increase of mean pulmonary arterial pressure and pulmonary vascular resistance as well as the ratio of right ventricular weight vs left ventricular plus septal weights. The results suggested that Ginkgo Plus could relieve the hypoxic pulmonary hypertension.

Animals↗
PubMed1996

Clinical and experimental studies on the treatment of senile constipation with shenshen wan.

From August 1988 through February 1991, we have successfully treated 400 cases of senile constipation with self-made Shenshen Wan with a total effective rate of 98%. A group of patients taking Maren Wan served as controls. Clinical practice has proved that Shenshen Wan can not only relax the bowels, but also improve renal function. Furthermore, no side effects whatever were observed after a prolonged administration of the pills.

Aged↗
PubMed1996

[Possible mechanism of the analgesic effect of interleukin-2 in central nervous system].

The monoclonal antibody against IL-2R (Tac) could not block the analgesic effect of IL-2, and IL-2 mutant that could not bind to beta subunit of IL-2 receptor still had capability of increasing the pain threshold of rats. All these facts suggest that the analgesic effect of IL-2 in CNS is not mediated through the IL-2 receptor, and that the immune and analgesic effects of IL-2 are mediated through different receptor mechanisms. It is suggested that there are common antigenic determinants and similar structure between IL-2 and endogenous opioid peptides (EOP). This implies that the analgesic effect of IL-2 might be mediated by interaction between IL-2 and opioid receptors in CNS. Using radioimmunoassay the contents of EOP of different nuclei were measured at different times after injecting IL-2 into the lateral ventricle of rats. The results suggested that the analgesic effect of IL-2 may be related to beta-EP and LEK in arcuate hypothalamic nucleus, paraventricular hypothalamic nucleus and locus ceruleus.

Analgesics, Non-Narcotic↗
PubMed1995

The myeloid zinc finger gene, MZF-1, regulates the CD34 promoter in vitro.

MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation. The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and, in the carboxy-terminus, 5 through 13. We previously identified the DNA consensus binding site recognized by the two DNA binding domains. To assess the transcription regulatory function of MZF-1, the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4. The expression vector was cotransfected with the chloramphenicol acetyl transferase (CAT) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3, 293, K562, and Jurkat cell lines. MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293. In contrast, MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat. The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation, including the CD34 promoter. MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines. Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays. MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines. As with the heterologous DNA binding domain, MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines. Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites. The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function.

3T3 Cells↗
PubMed1995

Altered immune responses in mice lacking inducible nitric oxide synthase.

Nitric oxide (NO) is important in many biological functions. It is generated from L-arginine by the enzyme NO synthase (NOS). The cytokine-inducible NOS (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of NO which can be cytotoxic. To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile and without evident histopathological abnormalities. However, in contrast to wild-type and heterozygous mice, which are highly resistant to the protozoa parasite Leishmania major infection, mutant mice are uniformly susceptible. The infected mutant mice developed a significantly stronger Th1 type of immune response than the wild-type or heterozygous mice. The mutant mice showed reduced nonspecific inflammatory response to carrageenin, and were resistant to lipopolysaccharide-induced mortality.

Amino Acid Oxidoreductases↗