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Biomedical subjects

M Zhao

Publications and source records attributed to M Zhao.

At least 289 records · Page 16Linked to original sources

The effects of isoflurane and halothane on blood flow and 31P NMR spectra in murine RIF-1 tumors.

The principal aim of these studies was to evaluate the utility of isoflurane and halothane for NMR investigations of tumor physiology. In vivo 31P and 2H NMR were used to examine RIF-1 tumors before, during, and (for 31P) after anesthesia. In tumors, halothane decreases blood flow, [PCR]:[NTP], and pH indicated by the Pi chemical shift (pHnmr), while it increases [Pi]:[NTP]; effects consistent with well-established cardiovascular effects of halothane. Isoflurane does not affect tumor blood flow or [PCr]:[NTP], but increases tumor [Pi]:[NTP] and decreases tumor pHnmr. In vivo 31P NMR measurements of normal mouse liver (upper abdomen) indicate that isoflurane has a similar effect in the liver. Although the mechanism for these effects is unknown, observation of a split Pi peak during isoflurane anesthesia suggests that a pool of Pi in a lower pH environment may become evident under isoflurane anesthesia. Regardless of the cause for increased [Pi]:[NTP] and decreased pHnmr, the utility of isoflurane anesthesia for 31P NMR studies of energy metabolism is limited.

Animals↗

The stability of amino acids at submarine hydrothermal vent temperatures.

It has been postulated that amino acid stability at hydrothermal vent temperatures is controlled by a metastable thermodynamic equilibrium rather than by kinetics. Experiments reported here demonstrate that the amino acids are irreversibly destroyed by heating at 240 degrees C and that quasi-equilibrium calculations give misleading descriptions of the experimental observations. Equilibrium thermodynamic calculations are not applicable to organic compounds under high-temperature submarine vent conditions.

Alanine↗

Kinetic analysis of cardiolipin synthase: a membrane enzyme with two glycerophospholipid substrates.

Mitochondrial cardiolipin synthase catalyzes the transfer of a phosphatidyl moiety from phosphatidyl-CMP (PtdCMP) to phosphatidylglycerol (PtdGro) in the presence of specific divalent cations. The synthase was solubilized from Saccharomyces cerevisiae mitochondria and purified about 300-fold. The partially enzyme was part of a medium-size, mixed micelle which had to bind to a foreign substrate/detergent micelle before catalysis could occur. The kinetics of cardiolipin synthase were studied by changing the molar fraction of substrate in the micelles. The enzyme obeyed Michaelis-Menten kinetics in relation to PtdCMP with a Km of 0.03 mol%. PtdGro caused sigmoidal kinetics with a low apparent affinity. It is speculated that it was involved in docking the enzyme to the substrate/detergent micelle. Cardiolipin synthase did not catalyze isotope exchange between [14C]CMP and PtdCMP, virtually excluding a ping-pong catalytic mechanism. Mg2+ stimulated the activity by increasing the turnover number rather than the substrate affinity, a mechanism which was also found for the Co(2+)-activation of rat liver cardiolipin synthase. It is concluded that a direct association of the metal ion and the enzyme forms the active cardiolipin synthase which has a very high affinity for PtdCMP and a lower affinity for PtdGro.

Animals↗

Determination of alpha-dialkylamino acids and their enantiomers in geological samples by high-performance liquid chromatography after derivatization with a chiral adduct of o-phthaldialdehyde.

Derivatization with o-phthaldialdehyde (OPA) and the chiral thiol N-acetyl-L-cysteine (NAC) is a convenient and sensitive technique for the HPLC detection and resolution of protein amino acid enantiomers. The kinetics of the reaction of OPA-NAC with alpha-dialkylamino acids was investigated. The fluorescence yield of alpha-dialkylamino acids was only about 10% of that of protein amino acids when the derivatization was carried out at room temperature for 1-2 min, which is the procedure generally used for protein amino acid analyses. The fluorescence yield of alpha-dialkylamino acids can be enhanced by up to ten-fold when the derivatization reaction time is increased to 15 min at room temperature. The OPA-NAC technique was optimized for the detection and enantiomeric resolution of alpha-dialkylamino acids in geological samples which contain a large excess of protein amino acids. The estimated detection limit for alpha-dialkylamino acids is 1-2 pmol, comparable to that for protein amino acids.

Acetylcysteine↗

T lymphocyte infiltration in the brain following anterior chamber inoculation of HSV-1.

Following inoculation of the KOS strain of herpes simplex virus type 1 (HSV-1) into one anterior chamber of euthymic BALB/c mice, virus spreads from the injected eye to the central nervous system and from the central nervous system to the optic nerve and retina of only the uninoculated eye. In contrast, in athymic BALB/c mice or mice depleted of both CD4+ and CD8+ T cells, virus spreads to the optic nerve and retina of both the injected eye and the uninjected eye. To determine the location in the central nervous system where spread of virus to the optic nerve and retina of the injected eye is prevented, euthymic BALB/c mice were injected with a mixture of KOS and RH116, a mutant of KOS that contains the Escherichia coli beta-galactosidase (beta-gal) gene. Several animals were sacrificed each day; serial frozen sections of the brain were prepared and sequential sections were stained for beta-gal or for T cells. At all sites except the suprachiasmatic nuclei, virus and T cells arrived at approximately the same time. However, at day 5 post inoculation (PI), T cells were present in both the ipsilateral and the contralateral suprachiasmatic nuclei, but only the ipsilateral suprachiasmatic nucleus was virus-positive. Since virus spreads from the ipsilateral suprachiasmatic nucleus to the contralateral optic nerve, these results suggest that T cells infiltrating the area of the contralateral suprachiasmatic nucleus prior to the arrival of virus at this site prevent virus spread into the optic nerve of the inoculated eye.

Animals↗

Small changes in cationic substituents of diphenylfuran derivatives have major effects on the binding affinity and the binding mode with RNA helical duplexes.

The interactions of dicationic, 2-4, and tetracationic, 5-7, diphenylfuran analogs of 1 (furamidine) with RNA have been analyzed by thermal melting, spectroscopic, viscometric, kinetic and molecular-modeling techniques. The results of these studies indicate that most of the furan derivatives bind to RNA duplexes by intercalation in contrast to their minor-groove binding mode in AT sequences of DNA, but similar to their binding mode in GC rich regions of DNA. The highest affinity for RNA is found for an imidazoline dication, 2. With some substituents which inhibit formation of a strong intercalation complex, the results suggest a non-intercalative type of binding occurs. The non-intercalative binding probably occurs through a complex with the furan derivative bound in the narrow, deep major groove of A-form RNA helices.

Amidines↗

Gene-targeted B-deficient mice reveal a critical role for B cells in the CD4 T cell response.

The role of B cells in promoting T cell responses is still controversial. In this study, we use JHD mice which have a targeted mutation in the JH gene and are thus rendered deficient in B cells to address this issue. We show here that immunization of JHD mice with soluble antigen fails to prime CD4 T cells, for either clonal expansion or delivery of immunological help for antibody responses. This lack of CD4 T cell priming in JHD mice corresponds to a 3- to 9-fold lower co-stimulatory activity of antigen-presenting cells (APC) from the JHD mice, as measured by anti-CD3-induced proliferative responses of CD4 T cells. This in turn is due to a defect of APC from JHD mice in response to T cell-mediated induction of co-stimulatory activity. As the development of macrophages and dendritic cells is unaffected in the JHD mice, our results demonstrate that B cells play a critical role in CD4 T cell priming, possibly by delivering a critical co-stimulatory activity for clonal expansion of CD4 T cells.

Animals↗

A study on immigrant labor in some enterprises in Shanghai.

"This article conducts analyses of the demographic characteristics, working conditions, and welfare of the immigrant laborers currently employed in some of the enterprises in Shanghai [China], based on survey data collected on the immigrant population at the end of 1993 and a sample survey in five enterprises in Shanghai. The article also makes suggestions for the future management and utilization of immigrant labor in Shanghai."

Asia↗

[Modifications of gene expression by tumor promoters].

The modifications of gene expression by tumor promoters were analyzed in vitro and in vivo. The results of slot blot hybridizations showed that tumor promoter TPA induced c-fos and c-myc expressions in mouse fibroblast cell line BALB/3T3 and rat liver, decreased the levels of Rb RNA in BALB/3T3 cell line and of alpha 1-I3 RNA in rat liver. It was also demonstrated that tumor promoter phenobarbital influenced c-fos and c-myc expressions and decreased alpha 1I3 mRNA level in rat liver during a long term experiment. Phenobarbital was found to have no effect on c-fos and c-myc expressions in rat liver during a short experiment. Tumor promoters induced the expressions of c-fos and c-myc which were positively-related to cancer formation and inhibited the expressions of Rb and alpha 1-I3 which were negatively-related to cancer formation. This implied that tumor promotion played an important role in cancer development and tumor promoters exerted their effects selectively according to the attributes of different genes.

3T3 Cells↗

[Isolation, purification and characterization of human proteinase inhibitor, alpha 2-macroglobulin].

A study of the isolation, purification and characterization of human proteinase inhibitor, alpha 2-macroglobulin (alpha 2-M) is presented. The alpha 2-M, with a purity of more than 90% and subunit molecular weight of 185kDa, was isolated by ammonium sulfate fractionated precipitation from human blood plasma and purified by DEAE cellulose DE52 column chromatography. It was found to be the same as the standard counterpart provided by sigma company. This purification procedure of alpha 2-M can be done with low cost, high efficiency and in large scale preparation.

Chromatography↗

Copper/zinc and manganese superoxide dismutase immunoreactivity in hepatic iron overload diseases.

Iron overload to the liver induces hepatic injury, eventually ending up with liver fibrosis or cirrhosis. Pathogenic mechanisms involved in liver damage are only partially known, but there is evidence for an important role of iron-induced reactive oxygen species. We have, therefore, analyzed the immunohistochemical reactivity for two major free radical scavengers, copper/zinc and manganese superoxide dismutase (Cu/Zn- and Mn-SOD's) in three situations of hepatic iron overload, and compared enzyme patterns with grades of iron deposition, grades of fibrosis, and levels of microphotometrically measured type IV collagen immunoreactivity. Cu/Zn- and Mn-SOD reactivity was detectable in hepatocytes with a heavy and a low iron burden, but Cu/Zn-SOD staining was more intense than that of Mn-SOD in the three groups analysed. There was trend for microphotometrically measured type IV collagen levels to increase with the amount of iron, and increased collagen IV was correlated with higher grades of Cu/Zn-SOD, but not of Mn-SOD, reactivity. The findings suggest that the two SOD's may be differentially expressed in states of hepatic iron overload, and that low expression of the inducible radical scavenger, Mn-SOD, may play a role in chronic iron toxicity.

Adult↗

Interferon-gamma-induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis.

BACKGROUND: The histopathology of multiple sclerosis (MS) is characterized by a loss of myelin and oligodendrocytes, relative preservation of axons, and a modest inflammatory response. The reasons for this selective oligodendrocyte death and demyelination are unknown. MATERIALS AND METHODS: In light of the T lymphocyte and macrophage infiltrates in MS lesions and the numerous cytokines these cells secrete, the direct influence of cytokines on survival of cultured oligodendrocytes and sensory neurons was investigated. Expression of cytokines in vivo was determined by immunolabeling cryostat sections of snap-frozen tissue containing chronic active lesions from four different patients. The samples were also analyzed for the presence of apoptotic nuclei by in situ labeling of 3'-OH ends of degraded nuclear DNA. RESULTS: The results showed: (i) interferon-gamma (IFN gamma) to be a potent inducer of apoptosis among oligodendrocytes in vitro and that this effect can be reversed by leukemia inhibitory factor (LIF); (ii) IFN gamma has a minimal effect on the survival of cultured neurons; (iii) IFN gamma at the margins of active MS plaques but not in unaffected white matter; (iv) evidence for apoptosis of oligodendrocytes at the advancing margins of chronic active MS plaques. CONCLUSIONS: Injury to a substantial number of oligodendrocytes in MS is the results of programmed cell death rather than necrotic cell death mechanisms. We postulate that IFN gamma plays a role in the pathogenesis of MS by activating apoptosis in oligodendrocytes.

Animals↗

[Biotherapy of advanced cancer by infusion of in vitro activated autolymphocytes].

Autolymphocyte biotherapy is an adoptive cellular therapy based upon the infusion of autologous lymphocytes that have been activated in vitro by anti-CD3 monoclonal antibody and depleted of suppressor T cells by cimetidine, indomethacin and low dose of gamma irradiation. The patients also receive oral cimetidine to block suppressor T cell activity in vivo. Sixty five patients received 217 autolymphocyte infusions and toxicity was minimal with transient fever and chill accompanying 18 infusions. The efficacy of treatment in patients received more than 3 infusions were evaluated. In 37 evaluable patients, the response rate (CR+PR) was 24% (9/37). As the side reactions are mild, the treatment can be done on an outpatient basis.

Adolescent↗

Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development.

Hodgkin disease (HD) is characterized by a small number of putative malignant cells [Hodgkin and Reed-Sternberg (HRS) cells] among a background of lymphocytes and histiocytes. The lineage of HRS cells is still elusive and a clonal origin of these rare cells has not formally been demonstrated. We isolated HRS cells by micromanipulation from histological sections of three cases of Hodgkin lymphoma (each representing a distinct subtype of the disease) and analyzed individual cells for immunoglobulin variable (V) gene rearrangements by PCR. In each of the three cases a single heavy-chain V (VH) (and in one case, in addition, a kappa light-chain) gene rearrangement was amplified from the HRS cells, identifying these cells as members of a single clone. A potentially functional VH rearrangement was obtained from a case of nodular sclerosis HD. Somatic mutations and intraclonal diversity in the VH genes indicate a germinal center B-cell origin of the HRS cells in a case of lymphocyte-predominant HD, whereas in a case of mixed-cellularity HD the sequence analysis revealed only nonfunctional V gene rearrangements, suggesting a pre-B-cell origin. This indicates that HRS cells can originate from B-lineage cells at various stages of development.

Adult↗