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Biomedical subjects

M Zhu

Publications and source records attributed to M Zhu.

At least 73 records · Page 4Linked to original sources
PubMed2001

A cellular gene up-regulated by hepatitis B virus-encoded X antigen promotes hepatocellular growth and survival.

Polymerase chain reaction (PCR) select complementary DNA (cDNA) subtraction of hepatitis B x antigen (HBxAg)-positive compared with -negative HepG2 cells resulted in the up-regulated expression of a cellular gene that encodes a transcript of 745 bases and a polypeptide 99 amino acids long. GenBank analysis revealed extensive homology with the amino terminal domain of cellular multidrug resistant proteins (MRP), although overexpression of this gene did not confer an MRP phenotype. In situ hybridization and immunostaining showed colocalized expression with HBxAg in the liver of hepatitis B carriers. Overexpression of this protein stimulated the growth of HepG2 cells in serum-free medium, and partially protected cells from anti-Fas-mediated killing, but did not promote growth in soft agar or tumor formation in nude mice. Introduction of the dominant negative inhibitor of nuclear factor kappaB (IkappaBalpha) into HBxAg-positive HepG2 cells decreased the levels of messenger RNA (mRNA) and protein, suggesting that its up-regulation is nuclear factor kappaB (NF-kappaB) dependent. Hence, HBxAg activation of NF-kappaB may result in the up-regulation of a cellular protein that promotes growth factor-independent survival and protects against Fas-mediated killing. This factor may contribute to the persistence of infected hepatocytes during chronic infection, which is important for the later development of hepatocellular carcinoma (HCC).

ATP-Binding Cassette Transporters↗
PubMed2001

Pharmacokinetics and system linearity of tea catechins in rat.

1. The pharmacokinetics and dose proportionality of three tea catechins were assessed. 2. Male Sprague-Dawley rats (210-230 g) received intravenous (i.v.) doses (50, 100, 200 and 300 mg kg(-1)) of a decaffeinated tea fraction containing (-)-epicatechin (EC: 5%), (-)-epigallocatechin gallate (EGCG: 50%) and (-)-epicatechin gallate (ECG: 13%). 3. Catechins in plasma, urine and faeces were quantitated by HPLC. 4. A two-compartment model was utilized to describe the bi-exponential disposition exhibited by the three catechins. 5. Over this dose range, the central distribution volume (Vc) for these catechins increased significantly (p < 0.05) from 0.17-0.34 to 0.42-0.66 l kg(-1). 6. A concentration-dependent increase in the plasma free fraction of catechins that mirrored the increases in Vc was observed. 7. The estimates of steady-state volume of distribution (Vss) were between 0.68 and 2.08 l kg(-1) at the lowest dose, and tended to increase with dose. 8. Appreciable amount of catechins partitioned into red blood cells (range 9-43%) and was apparently independent of concentration. 9. The mean elimination half-life (t(1/2,beta)) for EC, EGCG and ECG across doses were 43, 124, and 222 min respectively, and were invariant with dose. 10. Parallel to Vc, a 2-3-fold dose-dependent increase (p < 0.05) in systemic clearance (CL) was observed for the three catechins. 11. Urinary recovery was highest (21-31%) for EC, while those for EGCG and ECG was only approximately 3-5%. 12. Faecal recoveries of the catechins were between 0.5 and 5%. 13. In conclusion, the pharmacokinetics of the catechins appeared to be non-linear; dose-dependent changes in xenobiotic distribution might contribute to this observation.

Animals↗
PubMed2001

Multilineage cells from human adipose tissue: implications for cell-based therapies.

Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

Adipocytes↗
PubMed2001

ANG II-mediated inhibition of neuronal delayed rectifier K+ current: role of protein kinase C-alpha.

It was previously determined that ANG II and phorbol esters inhibit Kv current in neurons cultured from newborn rat hypothalamus and brain stem in a protein kinase C (PKC)- and Ca2+-dependent manner. Here, we have further defined this signaling pathway by investigating the roles of "physiological" activators of PKC and different PKC isozymes. The cell-permeable PKC activators, diacylglycerol (DAG) analogs 1,2-dioctanoyl-sn-glycerol (1 micromol/l, n = 7) and 1-oleoyl-2-acetyl-sn-glycerol (1 micromol/l, n = 6), mimicked the effect of ANG II and inhibited Kv current. These effects were abolished by the PKC inhibitor chelerythrine (1 micromol/l, n = 5) or by chelation of internal Ca2+ (n = 8). PKC antisense (AS) oligodeoxynucleotides (2 micromol/l) against Ca2+-dependent PKC isoforms were applied to the neurons to manipulate the endogenous levels of PKC. PKC-alpha-AS (n = 4) treatment abolished the inhibitory effects of ANG II and 1-oleoyl-2-acetyl-sn-glycerol on Kv current, whereas PKC-beta-AS (n = 4) and PKC-gamma-AS (n = 4) did not. These results suggest that the angiotensin type 1 receptor-mediated effects of ANG II on neuronal Kv current involve activation of PKC-alpha.

Alkaloids↗
PubMed2001

Chronotropic effect of angiotensin II via type 2 receptors in rat brain neurons.

Previously, we determined that angiotensin II (Ang II) elicits an Ang II type 2 (AT(2)) receptor-mediated increase of neuronal delayed rectifier K(+) (I(KV)) current in neuronal cultures from newborn rat hypothalamus and brain stem. This requires generation of lipoxygenase (LO) metabolites of arachidonic acid (AA) and activation of serine/threonine phosphatase type 2A (PP-2A). Enhancement of I(KV) results in a decrease in net inward current during the action potential (AP) upstroke as well as shortening of the refractory period, which may lead to alterations in neuronal firing rate. Thus, in the present study, we used whole-cell current clamp recording methods to investigate the AT(2) receptor-mediated effects of Ang II on the firing rate of cultured neurons from the hypothalamus and brain stem. At room temperature, these neurons exhibited spontaneous APs with an amplitude of 77.72 +/- 2.7 mV (n = 20) and they fired at a frequency of 0.8 +/- 0.1 Hz (n = 11). Most cells had a prolonged early after-depolarization that followed an initial fully developed AP. Superfusion of Ang II (100 nM) plus losartan (LOS, 1 microM) to block Ang II type 1 receptors elicited a significant chronotropic effect that was reversed by the AT(2) receptor inhibitor PD 123,319 (1 microM). LOS alone had no effect on any of the parameters measured. The chronotropic effect of Ang II was reversed by the general LO inhibitor 5,8,11,14-eicosatetraynoic acid (10 microM) or by the selective PP-2A inhibitor okadaic acid (1 nM) and was mimicked by the 12-LO metabolite of AA 12-(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraynoic acid. These data indicate that Ang II elicits an AT(2) receptor-mediated increase in neuronal firing rate, an effect that involves generation of LO metabolites of AA and activation of PP-2A.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2001

Defective morphogenesis and functional maturation in fetal islet-like cell clusters from OLETF rat, a model of NIDDM.

A failure in the compensate proliferation of pancreatic beta-cells, as the primary pathogenic event, has been reported in OLETF rat, a model of NIDDM. The aim of the present study is to define whether the beta-cell defect is attributed to the fetal stage islet development, if so, whether the defect involves down regulation of PDX-1 protein expression. Morphological changes, beta-cell function, and the expression of PDX-1 protein were examined in the cultured fetal islet-like cell clusters (ICCs) from OLETF rats along with their diabetes-resistant control counterpart LETO rats in the presence of 5.5 or 11.1mM glucose for 48, 72, 96, and 120-hr, respectively. We have observed four abnormalities in the ICCs of OLETF rats. First, a defective morphogenesis was noted during the 72 to 120-hr ICC culture, a period characterized by a dramatic increase in both beta-cell and non-beta-cell (alpha, delta, and PP) populations in control rats. This defective morphogenesis was demonstrated by a growth retardation of epithelial stratification and poor development of both beta-cell and non-beta-cell masses along with a parallel decline in relevant islet hormone contents. Second, a functional defect was characterized by failure to response to glucose during the 96 to 120-hr-cultured ICCs. Third, the ultrastructural analysis revealed a significant reduction in the number of secretory granules. Four, Western blot analysis showed a significant decrease of PDX-1 protein expression in the OLETF ICCs cultured in 11.1mM glucose for 48 to 72-hr and in 5.5mM glucose for 120-hr. Therefore, we concluded that during the fetal stage of islet development, OLETF rats exhibit both morphological and functional defects.

Animals↗
PubMed2001

Pharmacokinetics of para-aminosalicylic acid granules under four dosing conditions.

OBJECTIVE: To determine the pharmacokinetics and relative bioavailability of para-aminosalicylic acid (PAS) granules. DESIGN: Phase I pharmacokinetics study. SETTING: University of Arizona School of Pharmacy. PARTICIPANTS: Sixteen healthy male and female volunteers aged 36 +/- 8 years. INTERVENTIONS: Subjects received single doses of PAS granules (6 g) combined with cycloserine 500 mg, clofazimine 200 mg, ethionamide 500 mg, and pyridoxine 100 mg. Drugs were given on an empty stomach after an overnight fast (reference) with high-fat food, with orange juice, and with antacids. MEASUREMENTS AND RESULTS: Four subjects did not complete all four treatments due to adverse events or personal reasons. Plasma and urine samples were collected for 48 hours and measured by a validated HPLC assay. Pharmacokinetic data analysis was performed with WinNonlin using noncompartmental methods and a one-compartmental model. Bioequivalence testing was performed using the mean ratios of the maximum concentrations (Cmax) and AUC(0-infinity) of PAS, with 90% confidence intervals. Compared with the fasted condition, food increased Cmax 1.5-fold and AUC(0-infinity) 1.7-fold, and it doubled the time to maximum concentration (tmax). The least-squares mean ratios (treatment/reference) for Cmax were 0.90 (58% to 139% CI), 1.16 (75% to 179% CI), and 0.82 (52% to 127% CI) with orange juice, food, or antacid treatment, respectively. Corresponding ratios for AUC(0-infinity) were 1.05 (71% to 155% CI), 1.52 (103% to 224% CI), and 0.84 (57% to 125% CI), respectively. CONCLUSIONS: Food significantly enhanced the absorption of PAS, while orange juice and antacids had minor effects.

Adult↗
PubMed2001

Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids.

STUDY OBJECTIVES: To determine the effect of a high-fat meal, orange juice, and antacids on absorption of a single oral dose of cycloserine and to estimate its population pharmacokinetic parameters. DESIGN: Randomized, four-period, crossover study. SETTING: Clinical research center. PATIENTS: Twelve healthy volunteers. INTERVENTIONS: Subjects received single doses of cycloserine 500 mg after a 12-hour fast (reference), with a high-fat meal, with orange juice, and with antacids. They also received clofazimine 200 mg, ethionamide 500 mg, and p-aminosalicylic acid granules 6000 mg. MEASUREMENTS AND MAIN RESULTS: Plasma samples were collected for 48 hours and assayed by validated high-performance capillary electrophoresis assay. Concentration-time data were analyzed with noncompartmental, one-compartment, and population methods. The maximum concentration (Cmax) of cycloserine was decreased (p=0.02) by the high-fat meal. No other statistically significant differences were observed for Cmax and area under the curve from time zero to infinity across the four treatments. The high-fat meal significantly (p<0.0001) delayed time to maximum concentration by 4.7 times compared with that of the reference (1.1 hr). CONCLUSION: The pharmacokinetics of cycloserine were minimally affected by orange juice and antacids, whereas the high-fat meal delayed absorption. Administering cycloserine without a high-fat meal avoids potential alterations in the pattern of absorption.

Administration, Oral↗
PubMed2001

Population pharmacokinetics of intravenous and intramuscular streptomycin in patients with tuberculosis.

STUDY OBJECTIVES: To determine population pharmacokinetic parameters of streptomycin after administration of multiple intramuscular and intravenous doses. DESIGN: Prospective, unblinded clinical study. SETTING: Two medical centers in Denver, Colorado. PATIENTS: Thirty patients with tuberculosis. INTERVENTION: Patients received multiple doses of streptomycin as part of their tuberculosis treatment. They received concurrent drugs based on in vitro susceptibility data. MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over a 10-hour period and assayed by validated high-performance liquid chromatography Concentration-time data were analyzed using population methods. Streptomycin concentrations increased linearly with increasing intravenous doses. The intramuscular doses did not produce as linear a relationship, presumably because of variability in rates of and, potentially, completeness of absorption. Streptomycin elimination decreased with declining renal function. Higher, intermittent doses were well tolerated and appeared to maximize the peak concentration:minimal inhibitory concentration ratio. CONCLUSION: Overall, pharmacokinetic parameters of streptomycin were comparable with those previously published for streptomycin and other aminoglycosides. Higher, intermittent doses maximize pharmacodynamic parameter estimates and might have advantages for treatment of tuberculosis.

Adult↗
PubMed2001

[Estrogenicity of black cohosh (Cimicifuga racemosa) and its effect on estrogen receptor level in human breast cancer MCF-7 cells].

The estrogenicity of Black Cohosh (Cimicifuga racemosa, CR) was tested in vivo and in vitro and its effect on estrogen receptor (ER) level of human breast cancer MCF-7 cells were investigated. Based on the body weight of animals, 75, 150 and 300 mg/kg of CR were administered by tube feeding to immature female mice for 14 days. Estrus was observed and the uterine and ovary weights of mice were measured. The optimal dose of CR for the growth of MCF-7 cells was screened by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay. Subsequently, Growth curves of MCF-7 cells in blank control, 4.75 micrograms/L of CR and 0.3 nmol/L of 17 beta-estradiol groups were observed for 5 days. ER level in MCF-7 cells was analyzed by indirect immunofluorescence assay in flow cytometry. The results showed that uterine weight increased with the increasing dosage of CR and the days of estrus was significantly prolonged in the 300 mg/kg group (P < 0.05). The concentration of CR at 4.75 micrograms/L showed the strongest enhancement effects (64.7%). The doubling time (TD) of cell growth in CR group and 17 beta-estradiol group were 32.1 h and 31.7 h respectively, which were shorter than that of blank control (TD = 35.3 h). Additionally, 4.75 micrograms/L of CR significantly increased ER levels compared with the blank control (P < 0.01). Taking all the results together, CR has an estrogen-like action. The enhancing effect of CR on ER level is one of the potential mechanisms involved with its therapeutic role in climacteric syndrome.

Animals↗
PubMed2001

[Kinetics of interaction of H+ with constant and variable charge soils].

The kinetics of interaction of H+ ions with constant and variable charge soils were studied, among which changes of H+ concentration, positive surface charge and soluble Al with time and their influencing factors were investigated in detail. The results showed that the consumption processes of H+ ions in both constant and variable charge soils could be divided into fast and slow processes, but the manifestations and influencing factors were different for the two types of soils. The variations in positive surface charges for variable and constant charge soils, due to the difference in the contents of free Fe-oxides, are remarkably different and thus can not be modeled mathematically in the same manner for the two types of soils. The variations in soluble Al for both variable and constant charge soils were controlled by the components, solubility and solution kinetics of dominant clay minerals in soils, and could be described by both modified Elovich and two-constant rate equations mathematically.

Aluminum↗
PubMed2001

Liposome-C-erbB2 antisense oligodoxynucleotides in human ovarian cancer cells.

OBJECTIVE: To explore the effects of liposome-C-erbB2 antisense phosphorothioate oligodeoxynucleotides (S-ODNs) on C-erbB2 proto-oncogene expression and cell proliferation in human ovarian cancer cells. METHODS: The effects of liposome-C-erbB2 S-ODNs on C-erbB2 protein expression, cell cycle and cell proliferation in human ovarian cancer cells were studied by means of flow cytometry and 3H-thymidine incorporation. RESULTS: Liposome-C-erbB2 S-ODNs can specifically reduce C-erbB2 protein expression in human ovarian cancer cells, accompanied by a 30% inhibition of cell proliferation. The effectiveness of liposome-C-erbB2 S-ODNs on the expression of C-erbB2 was about 40 times higher than that of C-erbB2 S-ODNs. CONCLUSIONS: The data suggest that antisense therapy might be a useful method of gene therapy in ovarian cancer. The effectiveness of C-erbB2 S-ODNs could be greatly increased by adsorption of S-ODNs by liposomes.

Cell Cycle↗
PubMed2001

Study on action of acupuncture on ventromedial nucleus of hypothalamus in obese rats.

Effects of acupuncture on the spontaneous discharge of nerve cells and levels of monoamine neurotransmitters in ventromedial nucleus of hypothalamus (VMH) of the obese rats were investigated. Results indicated that the levels of tyrosine (Tyr) and dopamine (DA) were lowered, the levels of 5-hydroxytryptamine (5-HT) and 5-hydoxyindole acetic acid (5-HIAA) increased, and the frequency of the spontaneous discharge of nerve cells in VMH lowered in the obese rat group as compared with the normal group. When acupuncture obtained the effect of weight reduction, the frequency of spontaneous discharges of nerve cells in VMH were markedly increased, and the levels of Tyr, DA and tryptamine (Typ) and 5-HT/5-HIAA ratio elevated, and the 5-HT level lowered. It is suggested that the virtuous regulative action of acupuncture on VMH might be one of the key factors in acupuncture for weight reduction.

Acupuncture↗
PubMed2001

[Damage and economic threshold of the third generation of cotton bollworm in the Yangtze River basin cotton region of Jiangsu Province].

The impact of the third generation of cotton bollworm Helicoverpa armigera on shedding of buds and bolls and on bolling was studied by inoculating its larvae to cotton plants. The results showed that the shed rate of buds and bolls damaged by the larvae had the greatest impact on bolling, and its direct path coefficient was up to -0.8917. The larval population density and the number of buds and bolls damaged by the larvae impacted bolling mainly through the damaged shed rate during inoculating stage, and their indirect path coefficients were -0.8894 and -0.891 respectively. Both of the direct and indirect path coefficients of natural shed rate during inoculating stage to bolling were small, which showed that the cotton had little capacity of compensation while the third generation cotton bollworm occurring. The investigations of damage number by larvae showed that the damage equivalent of the 1st-6th instar larval were 0.02, 0.14, 0.31, 0.47, 0.84 and 1.54 old bolls respectively. Based on direct and indirect benefits from controlling, the economic threshold of the third generation of the bollworm was worked out to be 26 accumulated eggs per 100 plants.

Agriculture↗
PubMed2001

[Effect of toluene on urease activity of Lou soil].

Urease activity affected by toluene studying results showed as follows: Toluene had little action on Jackbean urease activity, but can remarkably increase soil urease activity in lower toluene concentrations and shorter time, the increasing variation was 1.48-3.96 times than without toluene treatment in seven soil samples tested. The variation was less than 3.98% when sterilized soil samples adsorbed the Jackbean urease. It may be because toluene can kill soil microorganism, release urease within cell and subsequently urease fixed into soil organic-inorganic colloidal. Different soil pH and microbiology can lead to vary differently for urease activity.

Fabaceae↗
PubMed2001

[The Immunophenotypical features of t (8; 21) (q22; q22) acute myeloid leukemia].

OBJECTIVE: To study the predictive value of immunophenotypical features in t (8; 21) (q22; q22) acute myeloid leukemia (AML). METHODS: Morphological/cytochemical, flow cytometric immunophenotyping, cytogenetic analyses (MIC) and RT-PCR were performed in 294 previously untreated AML. RESULTS: (1) In 294 AML patients, t (8; 21) AML were 21.8% (64); in AML-M(2), t (8; 21) AML were 54.7%; and in t (8; 21) AML, AML-M(2) were 81.3%. (2) Compared with control group, CD(19) and CD(34) expressions were higher, and CD(33) expression was lower (P < 0.001) in t (8; 21) AML. (3) If the cut-off value of CD(19) positive was >or= 20%, CD(19) positive rate was 13.6% (40/294) in AML, and 50% (32/64) and 3.5% (8/230) (P < 0.001) in t (8; 21) AML and control group. (4) CD(19)(+) and/or CD(34)(+) t (8; 21) AML accounted for 90.6% (58/64) of t (8; 21) AML and CD(19)(-)/CD(34)(-) for 9.6% (6/64). CONCLUSION: In t (8; 21) AML, especially M(2)/t (8; 21), CD(19) and CD(34) expressions were high. CD(19) was one of predictive markers of t (8; 21) AML.

Adolescent↗