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Biomedical subjects

M H Zhang

Publications and source records attributed to M H Zhang.

At least 19 recordsLinked to original sources
PubMed2005

Boosting partial least squares.

A difficulty when applying partial least squares (PLS) in multivariate calibration is that overfitting may occur. This study proposes a novel approach by combining PLS and boosting. The latter is said to be resistant to overfitting. The proposed method, called boosting PLS (BPLS), combines a set of shrunken PLS models, each with only one PLS component. The method is iterative: the models are constructed on the basis of the residuals of the responses that are not explained by previous models. Unlike classical PLS, BPLS does not need to select an adequate number of PLS components to be included in the model. On the other hand, two parameters must be determined: the shrinkage value and the iteration number. Criteria are proposed for these two purposes. BPLS was applied to seven real data sets, and the results demonstrate that it is more resistant than classical PLS to overfitting without loosing accuracy.

Algorithms↗
PubMed2005

Expression of survivin and bax/bcl-2 in peroxisome proliferator activated receptor-gamma ligands induces apoptosis on human myeloid leukemia cells in vitro.

The present study was undertaken to investigate the mechanisms of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligand-induced apoptosis on human myeloid leukemia K562 and HL-60 cell lines. The results revealed that both 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ) have significant anti-proliferation- and apoptosis-inducing effects on these two kinds of leukemia cells. Marked morphological changes of cell apoptosis including condensation of chromatin and nuclear fragmentation were observed clearly using Wright's and Hoechst 33258 staining. Reverse transcription-PCR and western blot analyses demonstrated that both survivin and bcl-2 expression were downregulated markedly, while bax expression was upregulated concurrently when apoptosis occurred. We therefore conclude that 15d-PGJ2 and TGZ have significant apoptosis effects on K562 and HL-60 cells in vitro, and that upregulation of bax as well as downregulation of survivin and bcl-2 expression may be the important apoptosis-inducing mechanisms. The results suggest that PPAR-gamma ligands may serve as potential therapeutic agents for both acute and chronic myeloid leukemia.

Antineoplastic Agents↗
PubMed2005

Oridonin-induced apoptosis in leukemia K562 cells and its mechanism.

Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one of the most important traditional Chinese herbal medicines. Recently oridonin has been reported to have anti- tumor effects in a large variety of malignant diseases. In this study, we investigated the apoptotic inducing effect of oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was measured using a microculture tetrazolium assay, apoptosis was measured by flow cytometry and electron microscopy as well as by DNA fragmentation analysis. Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and the expression of Bcl-2 and Bax proteins was detected by western blot analysis. The results showed that oridonin could inhibit the proliferation and induce apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2 expression was down- regulated, while Bax expression was up-regulated concurrently, when apoptosis ocurred. We therefore conclude that oridonin demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in vitro, and that changes in bcl-2 and bax protein levels as well as telomerase activity may play an important role in its mechanism of action.

Antineoplastic Agents↗
PubMed2001

Characterization of cholyl-leu-val-phe-phe-ala-OH as an inhibitor of amyloid beta-peptide polymerization.

Cholyl-LVFFA-OH (1, PPI-368) is an organic-modified peptide based on the sequence of amyloid beta-peptide (A beta). It is a potent and selective inhibitor of A beta polymerization that blocks the formation of neurotoxic species of A beta. In a nucleation-dependent polymerization assay of 50 microM A beta(1-40), equimolar concentrations of PPI-368 block polymerization based on turbidity and electron microscopy. Monomeric A beta(1-40) and A beta(1-42) are non-toxic when incubated with neuronal cell lines, but become toxic during polymerization. PPI-368 coordinately delays the onset of polymerization and the formation of neurotoxic A beta species for both peptides. In a polymerization extension assay seeded with pre-formed A beta polymer, similar inhibition and dose-dependency phenomena are observed with PPI-368. Radiolabeled PPI-368 is incorporated into fibrils during polymerization demonstrating binding to A beta peptide within afibrillar structure. Gel-filtration studies show progressive disappearance of A beta monomer and concomitant appearance of soluble higher molecular weight oligomers. In the presence of submolar concentrations of PPI-368, monomeric A beta is still present and oligomers are not observed PPI-368 does not inhibit the polymerization of other amyloidogenic proteins such as transthyretin (TTR) or islet amyloid polypeptide (IAPP(20-29).

Alzheimer Disease↗
PubMed2001

[Research on the selecting suspension cell line of higher productivity of flavonol glycoside by hypoxia stress as well as the stability in subcultures].

Investigate the influence of culture media to growth and flavonol glycoside synthesis of calli introduced from seedling of Ginkgo biloba. 6 cell lines were selected from calli by hypoxia stress. Among these cell lines the best one TZ-1 which growth index was 4.12 and the flavonol glycoside content was 1.25% in dried cell which was enhanced 257.1% compared with callus. The stability in subcultures was investigated: The average content of flavonol glycoside was 1.25% in dried cells and the growth index was 3.99 during 6 subcultures. Which variation coefficient was separately 0.065 and 0.048. The results show that hypoxia stress is a efficient method to select suspension cell line of higher productivity of flavonol glycoside.

Cell Hypoxia↗
PubMed1998

A novel photosensitizer, 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA). 1. Synthesis of 2-BA-2-DMHA and its phototoxicity to MGC803 cells.

The reaction of hypocrellin A (HA) with n-butylamine in pyridine under reflux leads to the formation of 2-butylamino-2-demethoxy-hypocrellin A (2-BA-2-DMHA), which is illustrated by ultraviolet-visible absorption spectra, proton nuclear magnetic resonance spectra, infrared spectra and mass spectra. The product exhibits stronger red-light absorption and has a much higher photopotentiation factor than HA (i.e., more than 200 versus four at a dose of 4 J cm-2 of red light on human gastric adenocarcinoma MGC803 cells). The mechanism of phototoxicity of 2-BA-2-DMHA on MGC803 cells irradiated with red light (lamada = 600-700 nm) has also been studied. An examination of extracted cellular DNA by agarose gel electrophoresis shows that the DNA has degraded into fragments with lengths which are multiples of approximately 180-190 base pairs (i.e., oligonucleosome size), a biochemical marker of apoptosis. Transmission electron microscopy reveals chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosis. This study suggests that 2-BA-2-DMHA is a potential photosensitizer and that its photoxicity to MGC803 cells proceeds via apoptosis.

Adenocarcinoma↗
PubMed1997

Phase I study of the antineovascularization drug CM101.

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.

Adult↗
PubMed1994

[Tumor necrosis factor gene expression in ovarian tumor].

The tumor necrosis factor (TNF) gene expression in ovarian tumor was observed with digoxigenin labeled TNF-alpha cDNA probes and in situ hybridization technique. 54 cases of fresh biopsies of the ovarian tumor and 10 cases of normal ovaries were snap frozen sectioned. The results showed that the average positive rate of TNF gene expression in some ovarian cells and tumor infiltrating lymphocytes (TIL) was higher than that in the borderline and benign tumor cells and TIL. The more advanced clinical stages, the higher does positive rate of TNF gene expression in the cancer cell and the smaller dose in the TIL. It was appeared that TNF gene expression of the tumor cells and TIL was connected with clinical stage and tissue typing of ovarian tumor. The data suggested TNF gene expression of cancer cell might play a role in the progress of ovarian cancer and as a marker of the advanced malignancy tumors. In addition, TNF gene expression of the TIL might mark the restinced state of the host immunology.

Adult↗
PubMed1993

Resistance to cyclopentenylcytosine in murine leukemia L1210 cells.

Cyclopentenyl cytosine (CPEC) exhibits oncological activity in murine and human tumor cells and has now entered Phase I clinical trials. Its mode of action as an antitumor agent appears to be inhibition by its triphosphate (CPEC-TP) of CTP synthase, the enzyme which converts UTP to CTP. In an attempt to elucidate the mechanism of resistance to CPEC, a murine leukemia cell line resistant to CPEC (L1210/CPEC) was developed by N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis and subsequent selection by cultivation of the L1210 cells in the presence of 2 microM CPEC. Resistant clones were maintained in CPEC-free medium for 6 generations before biochemical studies were performed. The resistant clone selected for further studies was approximately 13,000-fold less sensitive to growth inhibition by CPEC than the parental cells, and the concentration of CPEC required to deplete CTP in the resistant cells was 50-fold higher than in the sensitive cells. A comparison of the kinetic properties of CTP synthase from sensitive and resistant cells indicated alteration in the properties of the enzyme from the latter; the median inhibitory concentration for CPEC-TP increased from 2 to 14 microM, Km for UTP decreased from 126 to 50 microM, and Vmax increased 12-fold from 0.2 to 2.3 nmol/mg/min. Northern blot analyses of polyadenylated RNA from the resistant and sensitive cells indicated a 3-fold increase in transcripts of the CTP synthase gene in the resistant line. Consistent with these alterations in the properties of the enzyme, the resistant cells exhibited significantly expanded CTP and dCTP pools (4- 5-fold) when compared with the sensitive cells. No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells. These latter observations are most readily explained by feedback inhibition by the increased CTP levels of the resistant cells of uridine-cytidine kinase and/or of the membrane transport process used for initial entry of CPEC.

Animals↗
PubMed1993

[140 cases of acute leukemia caused by bimolane].

The cooperative group included 18 provincial and district hospitals. A retrospective study was carried out on 140 cases of therapy related leukemia (TRL) caused by bimolane (BML) for psoriasis from 1984 to 1992. This series of BML-TRL consists of 90 male and 50 female patients. 87.1% of them were from 20 to 50 years old. Annual incidence varied from 4 to 24 cases, and was maintained at this level through the period from 1986 to 1991 without any declining tendency. The average time interval between BML administration and diagnosis of leukemia was 46 months. 138 cases were diagnosed as ANLL and 2 cases were suspected of having ALL. Subtype frequency was shown as follows: M3 > M2 > M5 > M4 > M1 > M6. 67.1% of the patients had a low peripheral white blood cell counts (< 5 x 10(9)/L). 116 patients received chemotherapy. A 26.7% remission rate was obtained with 18.1% complete remission and 8.6% partial remission. A 115 day median survival was calculated through a follow up survey of 95 patients. Finally, we concluded that: (1) This has been the largest group of non-cancer-therapy-related-leukemia patients ever reported. This type of leukemia is characterized by a shorter latent period, higher remission rate less incidence of myelodysplastic syndrome and more frequent occurrence of leukopenia, as compared with other types of TRL. BML is supposed to be a strong leukemia-causing cytotoxic agent. Use of this drug in psoriasis and other benign diseases is not recommended.

Adult↗
PubMed1992

Study on the nanosecond transient absorption spectra of hypocrellin A.

In this paper, the nanosecond transient absorption spectra and the fluorescence spectra of Hypocrellin A(HA) are examined in solvents of varying polarity. There are three absorption bands in dilute HA solutions: Ia, IIa are defined as the triplet-triplet absorption of HA, the band IIIa is supposed to be the absorption of the solvent-separated ion pair (SSIP). In more concentrated solutions, only the absorption of SSIP was observed. The effects of solvent polarity on transient absorption spectra and fluorescence spectra of HA and the effect of oxygen on the intensities of the fluorescence of HA are discussed. Then a reasonable mechanism for the photolysis of HA is proposed.

Drugs, Chinese Herbal↗
PubMed1992

[Toxoplasmic retinochoroiditis].

Retinochoroiditis is a frequent ocular lesion in toxoplasmosis. It may be severe, and even lead to blindness. Sixteen cases of toxoplasmic retinochoroiditis verified through IFA were presented in this paper. Among these cases, 1 was of the multifocal type, its appearance being similar to that of the Coats disease; while the other 15 were of the focal type resembling to the central exudative retinitis (Rieger disease) or retinochoroidal scar. Serological finding of all the cases showed a positive IFA titer of > 1:80. A combination of pyrimethamine and sulfadiazine as well as spiramycin in addition to dexamethasone had been administered and proved effective. Since toxoplasmosis mostly occurs as latent and examination of the eye cannot differentiate from other causes of retinochoroiditis, so such clinical report of toxoplasmic retinochoroiditis was rare with particular reference in our country. The authors claimed that any individual presenting with retinochoroiditis suspected of toxoplasmosis should be subjected to serologic antibody test for establishing diagnosis.

Adolescent↗
PubMed1992

[Studies on the function of Ser579 and Arg580 in beta-subunit of penicillin G acylase with the method of site-specific mutagenesis].

According to the comparison of amino acid sequence between PGA (Penicillin G Acylase) and PBPs (Penicillin Binding Protein), We suggest that No. 565-595 peptide fragment in beta-subunit of PGA may be a substrate-binding site of enzyme. Plasmid pTZGA was constructed by cloning the 2.6 kb PGA gene of pWGA into phagemid pTZ18U The technique of site-specific mutagenesis was used to study the role of residue No. 579 (Ser) and No. 580 (Arg) of PGA. Four kinds of mutants were obtained (Ser579-->Gly579, Arg580-->Gly580, Arg580-->Glu580, Arg580-->Lys580), both Glu580 and Gly580 mutants showed no activity of enzyme and Lys580 mutant remained 30% and Gly579 mutant kept 70% activity of wilde type. The same protein expression of four mutants according to the results of ELISA indicate that mutation does not affect the expression of PGA, but Arg580 residue may be essential for substrate-binding or catalysis of PGA.

Amino Acid Sequence↗
PubMed1991

[Clinical diagnosis of aplastic anemia].

A study on the clinical diagnosis of aplastic anemia (AA) was carried out by using 5 different laboratory techniques including bone marrow aspiration and smear. Diagnosis of AA was established in 238 patients. Results with different methods were listed below: (1) Typical picture of AA was found in bone marrow smear of 196 patients. The positive rate was 82.4%. (2) Evaluation of marrow speckles might raise the positive rate to 89.9%. (3) Diagnosis of AA in 103 out of 110 patients was confirmed with bone marrow biopsy. The positive rate was 93.6%. (4) Typical 3-dimensional marrow tissue structure of AA was found in 68 out of 72 patients under scanning electron microscope, with a positive rate of 94.4%. (5) Total body bone marrow gamma-scintigraphy was performed in 56 patients; diagnosis of AA was reconfirmed in 54 patients with a positive rate of 96.4%. (6) 4 or 5 diagnostic techniques were used simultaneously in 30 patients with a positive diagnostic rate of 100%. The methodology of different techniques of bone marrow examination, the typical picture of AA and the causes of missing diagnosis were discussed with certain recommendations on each technique.

Adolescent↗
PubMed1990

Electronic spectra of hypocrellin A, B and their derivatives.

In this paper, the electronic spectra of hypocrellin A and B (HA and HB) are studied in detail. It has been proved that their three visible absorption bands come respectively from the pi pi transition of their conjugated systems and intramolecular proton transfer. In dilute solutions, their fluorescence spectra consist of the fluorescence peak of the neutral monomolecule and that of the zwitter-ions that are formed through proton transfer of excited states. In concentrated solution, the longer wavelength emission band is composed of the overlapped fluorescence peaks of zwitter-ions and excimers. The fluorescence spectra of the crystalline hypocrellin A and B consist of the fluorescence peaks of zwitter-ions and excimers and the fluorescence of neutral monomolecules could could not be observed. Their relative intensities are closely related to the excitation wave-length.

Benz(a)Anthracenes↗