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Biomedical subjects

M Zhu

Publications and source records attributed to M Zhu.

At least 235 records · Page 13Linked to original sources
PubMed1996

Application of radioligand receptor binding assays in the search for CNS active principles from Chinese medicinal plants.

Extracts of Schefflera bodinieri and S. delavayi (Araliaceae), Celastrus angulatus and C. orbiculatus (Celastraceae), Clerodendrum mandarinorum and C. bungei (Verbenaceae), Periploca callophylla and P. forrestii (Asclepiadaceae), Alangium platanifolium (Alangiaceae) and Uncaria rhynchophylla (Rubiaceae) were assessed for CNS activity against 18 radioligand receptor binding assays. The receptors used were alpha 1-, alpha 2- and beta-adrenoceptors, 5HT-1, 5HT-1A, 5HT-2, opiate, adenosine-1, benzodiazepine, Ca+2 channel, sulphonylureas, dopamine-1, dopamine-2, muscarinic, histamine-1, Na+/K+ ATPase, GABAA and GABAB. The results indicate that these ligand-receptor binding assays are useful for understanding the mode of action of herbal medicines and for bioassay guided fractionation of plant active ingredients.

Animals↗
PubMed1996

Chemical and biological investigation of the root bark of Clerodendrum mandarinorum.

A 70% EtOH extract of Clerodendrum mandarinorum root bark was assessed for CNS activity against 18 radioligand receptor binding assays. The results showed that the extract was able to bind to opiate, adenosine-1, alpha 2-adrenergic, 5HT-1, 5HT-2, dopamine-2, histamine-1, GABA(A), and GABA(B) receptors. Fourteen compounds were isolated and identified by El-MS, 1H-NMR and 13C-NMR spectra as known triterpenoids (friedelanone, lupeol, betulinic acid), steroids (24S-stigmata-5,25-dien-3 beta-ol,22E,24S-stigmata-5,22,25-trien-3 beta-ol), flavonoids (cirsimaritin, cirsimaritin-4'-glucoside, quercetin-3-methyl ether), tetra-hydro-alpha-pyrone and saccharides (sucrose, alpha-D- and beta-D-glucopyranose, ethyl-alpha-D-glucopyranoside, 2-ethyl-beta-D-fructofuranoside). The isolated compounds were assessed for activity by the radioligand receptor binding assays. Betulinic acid and ethyl-alpha-D-glucopyranoside showed weak activities against sulphonylureas (IC50 = 7.5 microM) and muscarinic receptors (IC50 = 5.5 microM), respectively. Cirsimaritin-4'-glucoside was weakly active in the adenosine-1 binding assay (IC50 = 3.0 microM), whereas seven structurally related flavonoids, not isolated from C.mandarinorum, were inactive.

Animals↗
PubMed1996

A comparison of values of annual limits on intake presented in ICRP 61 and 10 CFR part 20.

The latest (1991) major revision of the U.S. Nuclear Regulatory Commission regulations incorporates internal dose concepts and primary and secondary dose limits adapted from the recommendations of the International Commission on Radiation Protection Publication 30 published in 1979. This work compares values of the Annual Limits on Intake (ALIs) reported in the latest U.S. regulations with those recommended in the more recent, 1990, International Commission on Radiation Protection Publication 61. Overall trends in the updated ALI values compared to those in the regulations, as well as radionuclides exhibiting greater than +/-50% changes in these values, after correcting for differences in the primary dose limits, are reported.

Humans↗
PubMed1996

Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor, and alpha2-macroglobulin.

The goal of our studies was to learn about the mechanism of fibronectin degradation in chronic ulcers. We found that the appearance of fibronectin fragments in chronic ulcer wound fluid correlated with elevated levels of elastase and cleavage of the proteinase inhibitors alpha2-macroglobulin (alpha2-M) and alpha 1-proteinase inhibitor (alpha1-P1). Some wound fluid samples retained the capacity to degrade fibronectin in vitro. Degradation of fibronectin by these samples was blocked by specific inhibitors of neutrophil elastase but not by inhibitors of metalloproteinases. Addition of human neutrophil elastase to mastectomy fluid, an acute wound fluid, resulted in formation of alpha1-PI and alpha2-M complexes and cleavage products resembling those observed in chronic wound fluid. Moreover, degradation of fibronectin and processing of matrix metalloproteinase MMP-9 occurred under these conditions. Taken together, our findings suggest that elevated levels of neutrophil elastase are responsible for fibronectin degradation in the chronic wound environment.

Adult↗
PubMed1996

Intracellular expression of single-chain variable fragments to inhibit early stages of the viral life cycle by targeting human immunodeficiency virus type 1 integrase.

Integration of viral DNA into a chromosome of the infected host cell is required for efficient replication of a retroviral genome, and this reaction is mediated by the virus-encoded enzyme integrase (IN). As IN plays a pivotal role in establishing infection during the early stages of the retroviral life cycle, it is an attractive target for therapeutic intervention. However, the lack of effective antiviral drug therapy against this enzyme has led to the testing of other novel approaches towards its inhibition. In these studies, a panel of anti-human immunodeficiency virus type 1 (anti-HIV-1) IN hybridomas has been used in the construction of single-chain variable antibody fragments (SFvs). The monoclonal antibodies produced by these hybridomas, and derived SFvs, bind to different domains within IN. We now demonstrate that intracellular expression of SFvs which bind to IN catalytic and carboxy-terminal domains results in resistance to productive HIV-1 infection. This inhibition of HIV-1 replication is observed with SFvs localized in either the cytoplasmic or nuclear compartment of the cell. The expression of anti-IN SFvs in human T-lymphocytic cells and peripheral blood mononuclear cells appears to specifically neutralize IN activity prior to integration and, thus, has an effect on the integration process itself. These data support our previous studies with an anti-HIV-1 reverse transcriptase SFv and demonstrate further that intracellularly expressed SFvs can gain access to viral proteins of the HIV-1 preintegration complex. This panel of anti-HIV-1 IN SFvs also provides the tools with which to dissect the molecular mechanism(s) directly involved in integration within HIV-1-infected cells.

Amino Acid Sequence↗
PubMed1996

Binding of intracellular anti-Rev single chain variable fragments to different epitopes of human immunodeficiency virus type 1 rev: variations in viral inhibition.

Intracellular immunization to target the human immunodeficiency virus type 1 (HIV-1) regulatory protein Rev has been explored as a genetic therapy for AIDS. Efficient intracellular expression of rearranged immunoglobulin heavy and light chain variable regions of anti-Rev monoclonal antibodies, with various vectors, and subsequent inhibition of HIV-1 replication have been previously reported by our laboratories. To further understand the molecular mechanisms and effects that intracellular anti-Rev single chain variable fragments (SFvs) have against HIV-1, via blocking of Rev function, two anti-Rev SFvs which specifically bind to differing epitopes of the Rev protein have been cloned. One SFv binds to the Rev activation domain, and the second SFv binds to the distal C terminus of Rev in the nonactivation region. Further studies now demonstrate that both anti-Rev SFvs lead to variable resistance to HIV-1 infection. Although binding affinity assays demonstrated that the SFv which specifically recognizes the Rev activation domain (D8) had an extracellular binding affinity significantly lower than that of the SFv specific to the nonactivation region (D1O), the SFv D8 demonstrated more potent activity in inhibiting virus production in human T-cell lines and peripheral blood mononuclear cells than did SFv D10. Thus, extracellular binding affinities of an SFv for a target viral protein cannot be used to directly predict its activity as an intracellular immunization moiety. These data demonstrate potential approaches for intracellular immunization against HIV-1 infection, by efficiently blocking specific motifs of Rev to after the function of this retroviral regulatory protein. These studies extend the understanding of the effects, on a molecular level, of SFvs binding to critical epitopes of Rev and further suggest that rational design of SFvs, with interactions involving specific viral moieties which mediate HIV-1 expression, may hold promise for the clinical application of genetic therapies to combat AIDS.

Amino Acid Sequence↗
PubMed1996

Targeting human immunodeficiency virus type 1 reverse transcriptase by intracellular expression of single-chain variable fragments to inhibit early stages of the viral life cycle.

Novel molecular approaches to inhibit human immunodeficiency virus type 1 (HIV-1) infection have received increasing attention because of the lack of effective antiviral drug therapies in vivo. We now demonstrate that cells can be intracellularly immunized by cytoplasmic expression of single-chain variable antibody fragments (SFv) which bind to the HIV-1 reverse transcriptase (RT) enzyme. The expression of anti-RT SFv in T-lymphocytic cells specifically neutralizes the RT activity in the preintegration stage and affects the reverse transcription process, an early event of the HIV-1 life cycle. Blocking the virus at these early stages dramatically decreased HIV-1 propagation, as well as the HIV-1-induced cytopathic effects in susceptible human T lymphocytes, by impeding the formation of the proviral DNA. These data also demonstrate that intracellular, complete SFvs may gain access to viral proteins of the HIV-1 preintegration complex. These SFvs will provide a tool with which to better understand the molecular mechanisms involved in restricting viral replication in HIV-1-infected cells.

Animals↗
PubMed1996

Angiotensin II type 1 receptor modulation of neuronal K+ and Ca2+ currents: intracellular mechanisms.

Angiotensin II (ANG II) elicits an ANG II type 1 (AT1) receptor-mediated decrease in voltage-dependent K+ current (Ik) and an increase in voltage-dependent Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem. Modulation of these currents by ANG II involves intracellular messengers that result from an AT1 receptor-mediated stimulation of phosphoinositide hydrolysis. For example, the effects of ANG II on IK and ICa were abolished by phospholipase C antagonists. The reduction in IK produced by ANG II was attenuated by either protein kinase C (PKC) antagonists or by chelation of intracellular Ca2+. By contrast, PKC antagonism abolished the stimulatory effect of ANG II on ICa. Superfusion of the PKC activator phorbol 12-myristate 13-acetate produced effects on IK and ICa similar to those observed after ANG II. Furthermore, intracellular application of inositol 1,4,5-trisphosphate (IP3) elicited a significant reduction in IK. This suggests that the AT1 receptor-mediated changes in neuronal K+ and Ca2+ currents involve PKC (both IK and ICa) and IP3 and/or intracellular Ca2+ (IK).

Angiotensin II↗
PubMed1996

Poor capacity for proliferation of pancreatic beta-cells in Otsuka-Long-Evans-Tokushima Fatty rat: a model of spontaneous NIDDM.

Otsuka-Long-Evans-Tokushima Fatty (OLETF) rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the beta-cell proliferation per se is the primary pathogenetic event in OLETF rat. To determine whether it is, we used partially pancreatectomized rats as a model, with administration of phlorizin to control blood glucose level, to examine whether the capacity for proliferation of beta-cells during hyperglycemia or normoglycemia differs between OLETF and their diabetes-resistant counterparts, Long-Evans-Tokushima-Otsuka (LETO) rats. We also examined whether such a defect, if present, could be improved by nicotinamide. Male rats, 6 weeks of age, were allocated at random to two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into four subgroups by date of killing after surgery: 3-day, 7-day, 28-day (treated with phlorizin, nicotinamide, or saline), and 91-day. A sustained hyperglycemia was evident in the Px OLETF rats after surgery, which was associated with insufficient proliferation of beta-cells, characterized by decrease in beta-cell labeling index in proportion to decrease in beta-cell mass and reduction in insulin content in the remnant pancreas. This defect was unaffected by restoration of normoglycemia induced by phlorizin injection. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing beta-cell proliferation. These findings suggest that OLETF rats have poor capacity for proliferation of pancreatic beta-cells and that this change may be the critical pathogenetic event before the onset of overt diabetes.

Animals↗
PubMed1996

[A preliminary study on the relationship between Streptococcus and Neisseria,Veillonella in an artificial mouth model]

The viable cell count of monobacterial plaque of Streptococcus and mixed bacterial plaque of streptococcus and Neisseria Veillonella,also the demineralization caused by the plaques were observed.The assumption that Neisseria and Veillonella might reduce demineralization of enamel caused by streptococcus was confirmed.The relationship between streptococcus and Neisseria,Veillonella were preliminarily found out.

Journal Article↗
PubMed1996

[A study on the influence of zinc on the growth and metabolism of streptococcus in an artificial mouth model]

The influence of zinc on the growth and metabolism of Streptococcus was studied under controlled conditions in an artificial mouth model.the results confirmed the previous conclusion that zinc was capable of inhibiting the growth and metabolism of streptococcus both vivo and in vitro.At the same time,the feasibility of the imitative experiments in an artificial mouth model was proved.

Journal Article↗
PubMed1996

Gallium-67 scanning for detection of alveolitis in idiopathic pulmonary fibrosis and sarcoidosis.

OBJECTIVE: To investigate 67Gallium scanning for the detection of alveolitis in idiopathic pulmonary fibrosis and sarcoidosis. PATIENTS AND METHODS: 67Ga scintigraphy was performed in 14 patients with IPF (age: mean +/- s = 58.3 +/- 10.3 years), 13 patients with sarcoidosis (age: mean +/- s = 46.9 +/- 9.0 years) and 11 controls (age: mean +/- s = 44.0 +/- 10.5 years). RESULTS: Lung/thigh ratio was respectively 3.18 +/- 0.07 in IPF, 3.12 +/- 0.94 in sarcoidosis and 2.11 +/- 0.26 in controls. IPF and sarcoidosis groups had a significantly higher lung/thigh ratio comparing with the control group (P < 0.05). Three patients received 67Ga scanning examination after corticosteroid therapy and the 67Ga uptake decreased. CONCLUSIONS: The 67Ga scintigraphy is useful in monitoring the activity and extent of alveolitis.

Aged↗
PubMed1996

[Simple artificial mouth model].

A simple artificial mouth model is established under our laboratory condition. Development of monobacterial plaque and mixed bacterial plaque was studied in this artificial mouth model. The samples were subjected to viable count, microhardness measurement, etc. The result showed that the controlled conditions of the model can be used to study plaque development and earlier enamel lesion production on a time-dependent basis. It is concluded that the simple artificial mouth model is suitable for a wide range of dental applications.

Artificial Organs↗
PubMed1995

Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line.

Somatic mutation of the variable (V) regions of immunoglobulin genes occurs in vivo at rates that have been estimated to be between 10(-3) and 10(-4) per bp per generation. To study this process in vitro, the 18.81 pre-B-cell line and hybrids derived by fusing 18.81 to the NSO myeloma fusion partner were transfected with a mu heavy-chain construct containing a nonsense mutation in the V region (Vn) or the constant region (Cn). Mutation was quantitated by reversion analysis using the ELISA spot assay to detect single cells secreting IgM. Fluctuation analysis revealed that V-region mutations spontaneously occurred in 18.81 cells at an average rate of 5.8 x 10(-6) per bp per cell generation and in selected 18.81-NSO hybrids at greatly increased rates of 1.6 x 10(-3) to 5.8 x 10(-4) per bp per generation. The Vn construct also reverted frequently in transgenic mice, indicating that it contained sufficient information to mutate at high rates both in vivo and in vitro. Sequence analysis of reverted genes revealed that reversion was due to point mutations. Since the rates and nature of the mutations that are occurring in these transfected genes are similar to those reported in vivo, it should be possible to use this system to identify the cis-acting sequences and trans-acting factors that are responsible for V-region somatic hypermutation.

Amino Acid Sequence↗
PubMed1995

A well-differentiated B-cell line is permissive for somatic mutation of a transfected immunoglobulin heavy-chain gene.

pSV2neo plasmids containing an IgM heavy-chain gene with nonsense mutations in either the variable (V) or the constant (C) region were transfected into four differentiated mouse plasma cell lines: S107 and the NSO fusion partner (myeloma cell lines) and 2C3 and 36.65 (hybridoma cell lines). The frequencies of reversion of the nonsense mutations in multiple independent transfectants were determined with the spot ELISA and rates of reversion were calculated by fluctuation analysis. Mutations in both V and C regions were confirmed by sequence analyses. In the S107 cell line, spontaneous point mutations occurred in the V region at a rate of approximately 5 x 10(-5)/bp per cell generation, > 400-fold higher than the rate of V-region mutation in the NSO cell line and considerably higher than the rates in 2C3 and 36.65 hybridoma cell lines. These studies suggest that S107 is a relatively permissive cell line in which V-region mutations can occur constitutively, even though it represents a late stage of B-cell differentiation. Further, the results show that the construct used contains sufficient information in its flanking and coding sequences to allow a relatively high rate of V-region mutation, at least in the S107 cell line.

Amino Acid Sequence↗