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Y Z Zhao

Publications and source records attributed to Y Z Zhao.

15 recordsLinked to original sources
PubMed1998

Human ventricular myocytes in vitro exhibit both early and delayed preconditioning responses to simulated ischemia.

Myocardial tissue has been demonstrated to exhibit, in response to brief periods of ischemia, both an immediate period of cytoprotection [i.e. early or "first window" preconditioning response (EPR)], and a later period of cytoprotection [i.e. delayed or "second window" preconditioning response (DPR)], when exposed to a subsequent prolonged hypoxic insult. EPR has been documented in vitro in isolated cardiac myocytes, as well as in situ in intact hearts or trabeculae, for a number of vertebrate species, including humans. However, there are no reports to date of DPR in human cardiac myocytes. To address this question, human ventricular myocytes (HVM) primary isolates were prepared from fetal ventricular muscle, grown to confluency, and studied in primary culture in serum-free medium (> 90%) ventricular myocytes as determined by immunohistochemical analysis with an anti-myosin chain antibody). Using cell viability as determined by trypan blue exclusion, an EPR response could readily be detected following 15, 30, or 60 min of simulated ischemia (SI) in a hypoxic (< 1 tau pO2) buffer containing 11 mmol/l 2-deoxyglucose, followed by a prolonged (c. 17 h) SI challenge. In addition, HVM exposed to 60 min of SI, followed after 24 h by a period of SI, also exhibited a "second window" DPR (80 +/- 10% compared to 71 +/- 11% survival, in preconditioned and non-preconditioned cultures; P < 0.05; n = 18 independent experiments). Thus, in response to short periods of SI, human ventricular myocytes in vitro exhibit both "first window" and "second window" cytoprotective responses to subsequent, prolonged ischemic stress.

Analysis of Variance↗
PubMed1997

Screening solution-phase combinatorial libraries using pulsed ultrafiltration/electrospray mass spectrometry.

A method is described whereby a family of homologues is synthesized in a one-pot reaction, without isolation or purification, and the reaction mixture is screened using a competitive binding assay based on pulsed ultrafiltration/electrospray mass spectrometry (PUF/ESMS) to tentatively identify those derivatives having the highest affinity for a target receptor. As a model system to test this approach, a synthetic scheme designed to prepare a series of analogues of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), as diastereomeric mixtures, was carried out. Pulsed ultrafiltration screening of the crude reaction mixture against controls without protein detected protonated molecules corresponding to EHNA-type derivatives and three of its linear, alkyl homologues but did not show protonated molecules for an isobutyl or benzylic EHNA derivative, suggesting the latter was inactive. To verify this conclusion, we prepared E/THNA, the linear homologues, and the benzylic derivative (each as a diastereomeric mixture) and bioassayed them for them adenosine deaminase inhibition index ([I]/[S]0.5). The bioassay results for the individually synthesized analogues were in good agreement with that predicted by the observed relative ion enhancement in the PUF experiments. Thus, the PUF protocol might be used as a general method to quickly provide direction to the chemist in search of drug candidates.

Adenine↗
PubMed1997

Pulsed ultrafiltration mass spectrometry: a new method for screening combinatorial libraries.

In response to the need for rapid screening of combinatorial libraries to identify new lead compounds during drug discovery, we have developed an on-line combination of ultrafiltration and electrospray mass spectrometry, called pulsed ultrafiltration mass spectrometry, which facilitates the identification of solution-phase ligands in library mixtures that bind to solution-phase receptors. After ligands contained in a library mixture were bound to a macromolecular receptor, e.g., human serum albumin or calf intestine adenosine deaminase, the ligand-receptor complexes were purified by ultrafiltration and then dissociated using methanol to elute the ligands into the electrospray mass spectrometer for detection. Ligands with dissociation constants in the micromolar to nanomolar range were successfully bound, released, and detected using this method, including warfarin, salicylate, furosemide, and thyroxine binding to human serum albumin, and erythro-9-(2-hydroxy-3-nonyl)adenine binding to calf intestine adenosine deaminase. Repetitive bind- and-release experiments demonstrated that the receptor could be reused. Thus, pulsed ultrafiltration mass spectrometry was shown to provide a simple and powerful new method for the screening of combinatorial libraries in support of new drug discovery.

Adenine↗
PubMed1996

Two serologic markers to monitor the engraftment, growth, and treatment response of human leukemias in severe combined immunodeficient mice.

We have investigated human lactate dehydrogenase (LDH) isoenzymes and human nuclear matrix protein 41/7 (NMP 41/7) as potential serologic markers to monitor the course of human leukemia in severe combined immunodeficient (SCID) mice. Following the transplantation of 10(6) human acute lymphoblastic leukemia (ALL) Nalm-6 cells, human specific LDH isoenzymes were measurable in the serum of SCID mice as early as 7 days after transplantation, although serum total LDH increased in some animals as early as 5 days after transplantation. Human NMP 41/7 was measurable in all animals at day 15 after leukemia cell injection. Serum levels of total LDH, human specific LDH and NMP 41/7 increased progressively over time, reaching total LDH levels as high as 50,000 U/L at day 25 after transplantation. To determine whether the levels of LDH and NMP 41/7 in serum were a reflection of human tumor burden, we studied these serologic markers in SCID mice bearing measurable subcutaneous human neuroblastoma tumors, or compared the serum levels of these markers with the number of human leukemia CD10+ cells in the bone marrow of the SCID mice. The serum levels of total LDH, human specific LDH isoenzymes, and NMP 41/7 correlated well with tumor burden, and they drastically decreased or disappeared from serum after the human leukemia or neuroblastoma cells were selectively killed with a single intravenous (IV) injection of 1 to 3 micrograms diphtheria toxin (DT) (the cellular receptor for DT is present on human cells, but not on mouse cells). Paraplegic mice with central nervous system leukemia completely recovered after DT treatment. We conclude that measurements of serum levels of total LDH, human LDH isoenzymes, and NMP 41/7 are sensitive, quantitative, rapid, and easy to perform serologic methods useful to monitor the engraftment, progression, and treatment response of human leukemia in SCID mice.

Animals↗
PubMed1993

[Effect of different preparations of ginger on blood coagulation time in mice].

The experiments indicate that the decoction, ether extraction and suspension liquid of roasted ginger and charcoal of ginger all can markedly shorten the blood coagulation time in mice, while the decoction, ether extraction of fresh ginger and dry ginger cannot. The decoction of ginger charcoal has stronger effect than roasted ginger in shortening the blood coagulation time in mice. The effect of decoction of ginger charcoal on blood coagulation time tends to increase when the dosage is increased.

Animals↗
PubMed1987

Paraquat-induced cytoskeletal injury in cultured cells.

Although the redox cycling of paraquat (PQ) and the resultant "activated oxygen" generation are important in toxicity development, the intracellular events leading to cell injury remain unclear. To understand the mechanism of PQ-induced cell injury, we have studied the effects of PQ on DNA synthesis, cell proliferation, the cytoskeletal organization, particularly microtubules (MT) and microfilaments (MF), and the synthesis and composition of cytoskeletal proteins in mouse 3T3 cells. PQ treatment produced a dose-dependent inhibition of DNA synthesis and cell growth. Exposure of cells to PQ (313 microM, 20 hr) resulted in MT aggregation and bundling as well as MF redistribution in the perinuclear area as revealed by fluorescence microscopy. Although this PQ dose inhibited DNA synthesis by 95%, it caused only a 22% decrease in protein synthesis of the cytoskeletal fraction. Higher doses of PQ (1250 microM, 20 hr) caused (a) dramatic thinning out and loss of MT and (b) marked loss of MF cables and the appearance of numerous pine needle-like structures much finer and shorter than normal MF. Under these conditions, the synthesis of cytoskeletal proteins was decreased by about 83%. Further analysis of the cytoskeletal fraction from PQ-treated cells by sodium dodecyl sulfate gel electrophoresis showed (a) that tubulin was greatly diminished, in agreement with microscopic observations; (b) that two new protein bands appeared; and (c) another protein band which was also reduced considerably. These results indicate that the PQ-induced dose-dependent cytoskeletal injury may be important to the mechanism of cytotoxicity of this herbicide.

Actin Cytoskeleton↗
PubMed1981

SEM observations of the membranous structure of eggs from Taenia solium.

The shell of Taenia eggs are easily ruptured and lost if the eggs are prepared according to routine methods for SEM observation. As a result, only the vitelline layer is normally seen. When the uterus is fractured while frozen, the eggs located in the lateral uterine branches are exposed and do contain intact shells. In the fully developed eggs of T. solium, six layers surround the oncosphore. Starting from the outermost structure, they are the egg shell, the vitelline layer, the outer embryonic membrane, the middle embryophoric block layer, the inner basal membrane and the oncosphoral membrane, Numerous lacunae and capillaries from a fine tubular system in he embryophore. The functional significance of these structures is discussed. In addition two structures, which can be used to distinguish eggs of T. solium from those of T. saginatus are presented.

Animals↗
PubMed1981

The membranous structure of eggs of Ascaris lumbricoides as revealed by scanning electron microscopy.

The fine-structure of the egg shell and the oocyte of A. lumbricoides were examined with SEM. DMSO freeze fracture was used to obtain images of the eggs. Numerous filamentary fibers occur on the outer surface of the protein layer. These fibers are arranged in a network-like structure between the external projections of adjacent eggs. Twelve to 16 mammillated projections appear around the external periphery of each freeze fractured egg. Beneath the projection is a chitinous shell consisting of three layers; the outerlimiting membrane, the middle chitinous zone and the inner limiting membrane. Because the lipoid layer is dissolved by alcohol, it is not revealed with the freeze fracture technique. The oocyte is spherical or subspherical and possesses a continuous unit membrane. Particles, such as dense granules and refringent bodies, occur within the cytoplasm. Occasionally one or two first polar bodies, which will extrude into the perivitelline space, can be seen. The oocyte is frequently surrounded with a layer of deutoplasm.

Animals↗