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Biomedical subjects

Z Z Wu

Publications and source records attributed to Z Z Wu.

At least 19 recordsLinked to original sources

The syntheses and in vivo biodistribution of novel boronated unnatural amino acids.

A series of boronated, unnatural amino acids were prepared and their biodistribution determined in melanoma bearing mice. The unnatural amino acids were prepared utilizing recently developed borylation. The majority of the syntheses utilize metal catalyzed additions of diboron agents to unsaturated carbonyl compounds. Biodistribution studies in mice bearing melanoma tumors indicated that all the boronated amino acids were taken up by the melanoma tumors. The data for the cyclic five-membered ring analogue, 1-amino-3-boronocyclopentanecarboxylic acid, was most striking, exhibiting a nearly 22:1 ratio of boron concentration for tumor to brain at the 2 h time point, dropping to 7.3 after 6 h. The tumor to blood and tumor to skin ratios were also quite high. It is important to note that all of the amino acids were synthesized as racemic and diastereomeric mixtures. Thus there is a high probability that a single enantiomer of 1-amino-3-boronocyclopentanecarboxylic acid might exhibit far higher selectivity.

Amino Acids↗

[Inhibition of ATP-activated current by met-Enk in isolated DRG neurons of the rat].

The present study aimed to explore modulation of ATP-activated currents (I(ATP)) by met-Enk in rat DRG neurons. I(ATP) was recorded using the whole-cell patch clamp technique. The majority of the neurons examined responded to ATP (90.0 percent;, 45/50) with inward currents. In the 45 ATP sensitive neurons three kinds of responses to application of met-Enk were distinguished: (l) inward currents (29/45), (2) outward currents (9/45), and (3) no effect (7/45). Pretreatment with met-Enk (10(-9)~10(-5) mol/L) suppressed I(ATP) (10(-4) mol/L) in 29 neurons responding to met-Enk with inward currents. The inhibition by met-Enk of I(ATP) could be blocked by naloxone (10(-7) mol/L) in a concentration-dependent manner. Met-Enk of 10(-9), 10(-8), 10(-7), 10(-6) and 10(-5) mol/L suppressed I(ATP) by l3.2+/-5.4 percent; (n=5); 39.2+/-8.6 percent; (n=8), 54.l+/-8.6 percent; (n=8),43.3+/-7.9 percent; (n=7) and 43.l+/-7.9 percent; (n=7) (mean+/-MSE), respectively. A comparison of concentration - response relations of ATP with and without preapplication of met-Enk indicated that after pretreatment with met-Enk (10(-7) mol/L) the curve shifted downward markedly with a decrease of 25 percent; of the maximum value of I(ATP) and unchanged K(d) value. The suppression of I(ATP) by met-Enk was reversed as evidenced by intracellular dialysis of H-9 by using the repatch technique. Taken together, it is suggested that the inhibition by met-Enk of I(ATP) is caused by activation of opiate receptor, which eventually results in phosphorylation of ATP receptor, mediated by modulation of G protein coupling and intracellular signal transduction.

Adenosine Triphosphate↗

Comparison of the viscoelastic properties of normal hepatocytes and hepatocellular carcinoma cells under cytoskeletal perturbation.

The viscoelastic properties of both hepatocytes and hepatocellular carcinoma (HCC) cells were measured by means of a micropipette aspiration technique. Experimental results were analyzed with a three-element standard linear solid model, in which an elastic element, K1, is in parallel with a Maxwell element composed of another elastic element, K2, in series with a viscous element, mu. Further, we investigated the relevance of viscoelastic properties of these two types of cells to the cytoskeleton structures by treating cells with three cytoskeletal perturbing agents, namely cytochalasin D (CD), colchicine (Col) and vinblastine (VBL). The results showed that the elastic coefficients, but not viscous coefficient of HCC cells (K1 = 103.6 +/- 12.6 N m-2, K2 = 42.5 +/- 10.4 N m-2, mu = 4.5 +/- 1.9 Pa s, n = 30), were significantly higher than the corresponding values for hepatocytes (K1 = 87.5 +/- 12.1 N m-2, K2 = 33.3 +/- 10.3 N m-2, mu = 5.9 +/- 3.0 Pa s, n = 24). Upon treatment with CD, the viscoelastic coefficients of both hepatocytes and HCC cells decreased uniformly, with magnitudes for the decrease in elastic coefficients of HCC cells (K1: 68.7 to 81.7 N m-2, 66.3 to 78.9%; K2: 34.5 to 37.1 N m-2, 81.2 to 87.3%) larger than those for normal hepatocytes (K1: 42.6 to 49.8 N m-2, 48.7 to 56.9%; K2: 17.2 to 20.4 N m-2, 51.7 to 61.3%). There was a smaller decrease in the viscous coefficient of HCC cells (2.0 to 3.4 Pa s, 44.4 to 75.6%) than that for hepatocytes (3.0 to 3.9 Pa s, 50.8 to 66.1%). Upon treatment with Col and VBL, the elastic coefficients of hepatocytes generally increased or tended to increase while those of HCC cells decreased. The differences in either the pattern or the magnitude of the effect of cytoskeletal perturbing agent on the viscoelastic properties between HCC cells and hepatocytes might possibly reflect differences in the state of the cytoskeleton structure and function, or in the cells' sensitivity to perturbing agent treatment between these two types of cells. Changes in the viscoelastic properties of cancer cells might well affect tumor cell invasion and metastasis as well as interactions between tumor cells and their micro-mechanical environments.

Carcinoma, Hepatocellular↗

[Studies on non-anthraquinones in Rheum officinale Baill].

OBJECTIVE: To investigate the non-anthraquinones from the root and rootstock of Rheum officinale. METHOD: The chemical constituents were obtained from the 85% alcohol extract of the radix and rhizoma of R. officinale by column chromatography and identified by spectroscopic analysis. RESULT: Ten non-anthraquinones were obtained, of which eight were identified by spectroscopic analysis as rheosmine, daucosterol, d-catechin, 6-cinnamoylisolindleyin, (-)-epicatechin-3-O-gallate, resveratrol-4'-O-beta-D-(6"-O-galloyl)-glucopyranoside, gallic acid, D-sorbitol. CONCLUSION: Compounds rheosmine and D-sorbitol were obtained from the genus Rheum for the first time.

Plant Roots↗

The effect of superoxide dismutase on the recovery of human bone marrow hemopoietic stem cells stored at 4 degreesC.

The effect of superoxide dismutase (SOD) on the recovery of human hemopoietic stem cells stored at 4 degreesC has been studied. Human bone marrow cells from cancer patients without hemopoietic diseases were stored at 4 degreesC for 1-7 days in RPMI 1640 medium containing 10% human AB serum with or without 6 U/ml of SOD. The recovery of colony-forming units of the following types were counted: granulocyte and macrophage type; megakaryocyte type; mixed granulocyte, erythrocyte, megakaryocyte, and macrophage type; and burst-forming units of erythrocytic type. The SOD groups recovered, respectively, 5.6, 5.3, 4.6, and 4.4 times as many colonies as the control group. This study demonstrates that the addition of SOD to hypothermic storage media may increase the recovery of hemopoietic stem cells.

Cell Survival↗

[Studies of a 35 KDa substance from human fetal liver on the regulation of hematopoiesis].

About 30%-40% of hematopoietic stem cells in human fetal liver of 3-5 months are in S phase of cell cycle, much higher than the ratio of 10% of that in adult bone marrow. The existance of highly active hematopoietic stem cell proliferation stimulators is probably its molecular basis. CFU-S "suicide rate" in rats was adopted to detect the effective substance. Through several steps of separation, we obtained a relatively purified substance of 35 kDa, termed it as FLS-4. CD 34 positive cord blood cells were sorted and assayed for their response to FLS-4 in 3H-TdR incorporation assay. The response to FLS-4 alone was approximately 1 times the background response seen with no factor added. In combination with IL-6 and IL-3 produced response that was 2.9 and 6.5 fold respectively greater than that observed with no factor added, but was weakly in comparison with the effects of SCF. In combination with GM-CSF or IL-3, FLS-4 can stimulate the formation of blast-colonies. The results indicate that the FLS-4 is very likely to be a novel hematopoietic stem cell proliferation stimulator. In physical or biological characteristics, it exhibited a unique character different from IL-3, IL-6, GM-CSF, SCF or FLT3 ligand those are known to have hematopoietic stem cell proliferation stimulating activity. During the period of active hematopoiesis in fetal liver, FLS-4 might be the candidate in triggering hematopoietic stem cells from resting G0 to S phase.

Animals↗

[Studies on characteristics of proliferation and differentiation of hematopoietic stem cells in mice].

By using Y chromosome specific sex-determining region (Sry) as a new cytogenetic marker and PCR technique, the characteristics of proliferation and differentiation of hematopoietic stem cells in mice were studied. Bone marrow cells from male mice were injected into lethally-irradiated female mice, PCR results indicated that all of the CFU-S were originated from donor. It was found that CFU-S was able to proliferate and differentiate into various hematopoietic cells in vivo during its transplantation. Whereas the fibroblasts within donor CFU-S and the fibroblasts from bone marrow in recipient mouse reestablished by donor CFU-S were shown to be originated from the recipient. The above data demonstrated that CFC-S from bone marrow in mice possessed the characteristics of hematopoietic stem cells but was not prone to differentiate into fibroblasts.

Animals↗

[Studies on the isolation, structure identification and biological function of two tumor cell suppressors of human fetal liver origin].

Our previous work showed the existence of low molecular weight tumor suppressors in human fetal tissues. In this paper, two tumor cell suppressors were isolated and purified from methanol extract of human fetal liver by C18 reversed-phase medium pressure chromatography, gel filtration on Sephadex LH-20, and high-performance liquid chromatography, directed by suppression of growth of HL-60 cells. The structures of the suppressors were identified to be 7-ketocholesterol and 7-beta-hydroxycholesterol. Under the condition of in vitro agar plate culture, 7-ketocholesterol and 7-beta-hydroxycholesterol showed preferentially inhibitory effects on the growth of both human and murine leukemic cell lines including human HL-60 and murine S-180 cells, but less effective on the growth of normal human and murine bone marrow granulocyte-macrophage progenitors (CFU-GM).

Animals↗

[In vitro stimulation of HTC hepatoma cell growth by recombinant human augmenter of liver regeneration (ALR)].

It was demonstrated that biologically active ALR could be expressed from its cDNA in transient expression experiments in cos-7 cells. The results showed that the cytosolic fraction from the transfected cells with constructed plasmids DNA stimulated of DNA synthesis of in vitro HTC cells in a dose dependent manner. This finding suggests that the HTC hepatoma cell line may be used as a target for bioassay of human ALR in vitro.

Carcinoma, Hepatocellular↗

[Increase in the level of augmenter of liver regeneration mRNA in the rat regenerating liver after partial hepatectomy].

Augmenter of liver regeneration (ALR) is a novel hepatic stimulator. After 70% of the rat liver was removed, ALR-like activity in the remnant liver began to increase within 24 h. In parallel with the activity, the ALR mRNA level in the remnant liver increased 12 h after the operation and reached a maximum in 24 h. These findings indicate that the liver itself produces ALR, which may be a hepatotropic factor acting as a trigger for liver regeneration.

Animals↗

[The effect of GM-CSF/IL-3 on the grafting efficiency of CD34+ hemopoietic progenitor cells from umbilical cord blood].

CD34+ cells were isolated from human umbilical cord blood by using a high-gradient magnetic cell sorting system with anti-CD34 monoclonal antibody coated with microbeads, and then inoculated onto a pre-formed irradiated bone marrow stroma to evaluate the grafting efficiency of CD34+ cells with rhGM-CSF or IL-3, alone or in combination. The results showed that only 36% CD34+ cells in the control, and 68 - 89.6% in the groups with growth factors treatment seeded to the stroma. A short incubation of CD34+ cells with growth factors could rapidly reconstitute a long-term hemopoiesis in the long-term liquid culture system. This demonstrates that a brief treatment of CD34+ cells with GM-CSF or IL-3 can improve the grafting efficiency of transplanted umbilical cord blood cells.

Adult↗

[A method of measuring iris radius by computerized image analysis].

A new method of measuring the iris contour has been set up with a personal computer. The model of a parabolic curve, an approximate mimic iris contour curve, was traced to define the profile contour of the iris from a photograph. A radius measured from the apex of the curvature of the parabola, named iris radius (IR), was calculated by a computer to describe the degree of the curvature of the iris contour. The iris radius of 93 eyes of 68 cases with early pupillary block primary angle closure glaucoma were measured by this method. The results show that the mean iris radius of cases with glaucoma is shorter than that of the normal age matched controls (53 cases 106 eyes) and there is statistical significant difference (P < 0.01). This method of measurement can be an effective method to further study the early diagnosis and pathogenic mechanism of the pupillary block angle closure glaucoma.

Adult↗