Biomedical subjects

M Zhu

Publications and source records attributed to M Zhu.

At least 199 records · Page 11Linked to original sources

PubMed1998

[A bacteriology analysis from infected root canals of human deciduous teeth]

OBJECTIVE: To provide a basis for therapy and prevention, the flora of infected root canals of human deciduous teeth was analyzed.METHODS: By immediate-enzyme method, the bacteria compositions of 22 cases with infected root canals of deciduous teeth, including 8 cases with acute periapical inflammation and 14 with chronic ones, were examined. RESULTS: Among 240 strains bactera, 200 strains were obligate anaerobes, belonging to the genera peptostreptococcus, bacteriodes, veillonella, eubacterrum, propionibacterium, actinomyces and fusobacterium. Bacteriodes and eusobacterium especially B. gingivalis and F. nucleatum have been more frequently isolated from root canals with acute periapical inflammation than that with chronic ones (P<0.05). In chronic cases, veillonella especially V. parvula, were more frequently isolated than acute inflammation. CONCLUSION: Periaplcal inflammation of deciduous teeth was mixed polymicrobial infections regardless of acute or chronic cases and anaerobic bacteria were dominated. B. gingivalis and F. nucleatum probably were related to acute periapical inflammation of deciduous teeth. The effect of V. parvula on chronic periapical innammation of deciduous teeth should not be neglected.

Journal Article↗

PubMed1998

[The evaluation of computer-aided simulating system in orthognathic surgery]

OBJECTIVE: The purpose of this study is to evaluate the reliabillty of computer-aided simulating system for orthognathic system. METHODS: 24 cases with dentofacial deformities were undergone treatment of orthognathic surgery.The presurgical cephalograms and profiles were input to the computer and were digitized.The simulated profiles and cephalometric analysis were obtained by the simulating system,and computer with the actual posttreatment cephalograms. RESULTS: The prodicted and actual posttreatment soft tissue line drawings were quite similar in all areas except for the lower lip region. CONCLUSION: In all cases,the actual images were judged more esthetic than the predicted images. It allayed the fears that the computer generated predictions were unrealistically and ideal.

Journal Article↗

PubMed1998

[The antibacterial efficacy to obligate anaerobes isolated from the infected root canal of deciduous teeth]

OBJECTIVE:The antibacterial efficacy of 7 kinds drugs to 4 kinds obligate anaerobes isolated from the infected canal of deciduous teeth and 4 kinds standard strains was tested.The results showed that FC,Metronidazole,Chloromycin,Cefradium have strong antibacterial effects on experimental strains,but Erythromycin and Norvancomycin Hydrochloridum were not so effective.

Journal Article↗

PubMed1998

Preventive effects of selenium-enriched spiruline (SESP) on radiation pneumonitis.

We studied the early effects of selenium-enriched spiruline (SESP) on radiation-induced pulmonary fibrosis using histopathology, cDNA-mRNA dot-blot hybridization, and a biochemical technique for quantifying the hydroxyproline content. We found marked lung injury in the irradiated group, whereas only slight hyperemia, hemorrhage, exudation, and thickness of the interalveolar wall in the lung in the selenium-treated group. The hydroxyproline (hyp) content in the lungs and the synthesis of type III collagen mRNA decreased in the SESP-treated group. Selenium-enriched spiruline may have a protective effect on the development of radiation pneumonitis.

Animals↗

PubMed1998

Effect of partial pancreatectomy on beta-cell mass in the remnant pancreas of Wistar fatty rats.

Wistar fatty rat, which has been established by transferring the fa gene of Zucker fatty rat to the Wistar Kyoto rat, has many features in common with human NIDDM. It exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance. It is unclear, however, whether a defect in the beta-cell proliferation is related to the onset of diabetes mellitus together with insulin resistance in this model rat. To determine this, we compared non-fasting plasma glucose levels, insulin content and beta-cell mass in the remnant pancreas of Wistar fatty rats with those in their diabetic-resistant lean counterparts after a 70% partial pancreatectomy. We also examined whether such a defect, if present, could be improved by either phlorizin or nicotinamide. We further investigated if there were any differences in these parameters between the phenotypically identical but genotypically different Wistar lean rats with a gene type of homogeneous Fa/Fa and that of heterogeneous Fa/fa. Male rats, 6 weeks of age, were allocated at random into two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). A sustained hyperglycemia was evident in the Px Wistar fatty rats after surgery, which was accompanied by a reduction of insulin content and beta-cell mass in the remnant pancreas. The changes in insulin content and beta-cell mass were unaffected by restoration of normoglycemia, induced by phlorizin injection. The administration of nicotinamide partially ameliorated the sustained hyperglycemia by a slight but not significant increase in beta-cell mass. No discernible difference in the above parameters was observed between the Wistar lean rats with Fa/Fa and those with Fa/fa. These findings suggest that Wistar fatty rats have a poor capacity for proliferation of pancreatic beta-cells, which causes the onset of overt diabetes along with insulin resistance due to extreme obesity.

Animals↗

PubMed1997

Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen.

A vaccination strategy designed to enhance the immunogenicity of self-antigens that are overexpressed in tumor cells is to identify and slightly modify immunodominant epitopes that elicit T-cell responses. The resultant T cells, however, must maintain their ability to recognize the native configuration of the peptide-MHC interaction on the tumor cell target. We used a strategy to enhance the immunogenicity of a human CTL epitope directed against a human self-antigen, which involved the modification of individual amino acid residues predicted to interact with the T-cell receptor; this strategy, moreover, required no prior knowledge of these actual specific interactions. Single amino acid substitutions were introduced to the CAP1 peptide (YLSGANLNL), an immunogenic HLA-A2+-binding peptide derived from human carcinoembryonic antigen (CEA). In this study, four amino acid residues that were predicted to potentially interact with the T-cell receptor of CAP1-specific CTLs were systematically replaced. Analogues were tested for binding to HLA-A2 and for recognition by an established CTL line directed against CAP1. This line was obtained from peripheral blood mononuclear cells from an HLA-A2+ individual vaccinated with a vaccinia-CEA recombinant. An analogue peptide was identified that was capable of sensitizing CAP1-specific CTLs 10(2)-10(3) times more efficiently than the native CAP1 peptide. This enhanced recognition was shown not to be due to better binding to HLA-A2. Therefore, the analogue CAP1-6D (YLSGADLNL, Asn at position 6 replaced by Asp) meets the criteria of a CTL enhancer agonist peptide. Both the CAP1-6D and the native CAP1 peptide were compared for the ability to generate specific CTL lines in vitro from unimmunized apparently healthy HLA-A2+ donors. Whereas CAP1 failed to generate CTLs from normal peripheral blood mononuclear cells, the agonist peptide was able to generate CD8+ CTL lines that recognized both the agonist and the native CAP1 sequence. Most importantly, these CTLs were capable of lysing human tumor cells endogenously expressing CEA. The use of enhancer agonist CTL peptides may thus represent a new efficient direction for immunotherapy protocols.

Amino Acid Sequence↗

PubMed1997

Sequence dependent hypermutation of the immunoglobulin heavy chain in cultured B cells.

The variable (V) regions of immunoglobulin heavy and light chains undergo high rates of somatic mutation during the immune response. Although point mutations accumulate throughout the V regions and their immediate flanking sequences, analysis of large numbers of mutations that have arisen in vivo reveal that the triplet AGC appears to be most susceptible to mutation. We have stably transfected B cell lines with gamma2a heavy chain constructs containing TAG nonsense codons in their V regions that are part of either a putative (T)AGC hot spot or a (T)AGA non-hot spot motif. Using an ELISA spot assay to detect revertants and fluctuation analysis to determine rates of mutation, the rate of reversion of the TAG nonsense codon has been determined for different motifs in different parts of the V region. In the NSO plasma cell line, the (T)AGC hot spot motif mutates at rates of approximately 6 x 10(-4)/bp per generation and approximately 3 x 10(-5)/bp per generation at residues 38 and 94 in the V region. At each of these locations, the (T)AGC hot spot motif is 20-30 times more likely to undergo mutation than the (T)AGA non-hot spot motif. Moreover, the AGA non-hot spot motif mutates at as high a rate as the hot spot motif when it is located adjacent to hot spot motifs, suggesting that more extended sequences influence susceptibility to mutation.

Animals↗

PubMed1997

In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen.

BACKGROUND: Protein antigens are presented to cytotoxic T lymphocytes as small peptides (approximately 9-10 amino acids long) bound to class I molecules of the major histocompatibility complex. The identification of tumor-associated antigens and specific peptide epitopes (i.e., antigenic determinants) may be useful in the development of anticancer vaccines. The generation of a cytotoxic T-cell response to one peptide epitope (amino acids 146-154) of human prostate-specific antigen (PSA) has been reported. PURPOSE: Our aim was to identify novel PSA peptides capable of eliciting specific cytotoxic T-cell responses. METHODS: Candidate peptides were identified on the basis of the following criteria: 1) they contained consensus amino acid motifs for binding to HLA-A2, which is the most common type of class I molecule; 2) they lacked strong homology with PSA-related kallikrein proteins; and 3) they were capable of stabilizing HLA-A2 class I molecules on the surface of human T2 (transport deletion mutant) cells, which are defective in antigen presentation. T-cell lines capable of killing (i.e., lysing) T2 target cells that had been pulsed with specific PSA peptides were generated from three different males (two disease-free individuals and one patient with prostate cancer) by incubating peripheral blood mononuclear cells with the peptides and interleukin 2. Specific cell lysis was monitored by the release of radioactivity from target cells that had been labeled with [111In]oxyquinoline. RESULTS: Two novel PSA peptides capable of eliciting cytotoxic T-cell responses were identified; these peptides were designated PSA-1 (amino acids 41-150) and PSA-3 (amino acids 154-163). Four different cytotoxic T-cell lines were generated in response to these peptides-three against PSA-3 and one against PSA-1. Specific lysis of peptide-pulsed T2 cells by the T-cell lines was blocked by the addition of a monoclonal antibody directed against class I molecules. The T-cell lines were also capable of lysing PSA-positive, HLA-A2-positive LNCaP cells (human prostate carcinoma cells). The specificity of LNCaP cell lysis was shown by the following: 1) the inability of added human K562 (chronic myelogenous leukemia) cells to inhibit it, 2) the ability of added anti-HLA-A2 antibodies to block it, and 3) the inability of the T-cell lines to induce substantial lysis of PSA-negative, HLA-A2-positive human cancer cells. IMPLICATIONS: Our studies form a rational basis for the use of PSA peptides or recombinant vectors encoding PSA in the development of anticancer vaccine immunotherapy protocols for patients with prostate cancer.

Cell Line↗

PubMed1997

Integrity of p53 in hepatitis B x antigen-positive and -negative hepatocellular carcinomas.

Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection. Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.

Carcinoma, Hepatocellular↗

PubMed1997

Characterization of glutathione conjugates of pyrrolylated amino acids and peptides by liquid chromatography-mass spectrometry and tandem mass spectrometry with electrospray ionization.

High-performance liquid chromatography (HPLC) coupled with electrospray mass spectrometry (ES-MS) and tandem mass spectrometry (MS-MS) was used to identify the products formed upon reaction of lysine-containing peptides with the neurotoxicant 2,5-hexanedione (2,5-HD). In addition, secondary autoxidative reaction products of the resultant alkylpyrroles with the biological thiol, glutathione, were characterized. ES mass spectra of the HPLC-separated conjugates showed intense [M+H]+ ions as well as several ions formed by amide and C-S bond cleavage. The glutathione conjugates of pyrrolylated amino acids and peptides were analyzed by ES ionization and MS-MS, and product-ion spectra showed fragmentation pathways typical of glutathione conjugates. ES-MS-MS analysis of a synthetic nonapeptide modeling a sequence found in neurofilament proteins showed pyrrole formation after incubation with 2,5-HD, and sequence ions were used to assign the position of the pyrrole adduct. Subsequent reaction of the pyrrolylated peptide with reduced glutathione was evidenced by a shift in m/z of the sequence ions of the reaction products with or without prior methylation. The results demonstrate the utility of ES-MS and ES-MS-MS in the characterization of xenobiotic-modified peptides and confirm that stable pyrrole-thiol conjugates are formed by the reaction of biological thiols with pyrrolylated peptides.

Amino Acids↗

PubMed1997

Capillary isoelectric focusing.

Capillary isoelectric focusing (CIEF) provides excellent resolution of proteins with the advantage that separations are carried out in a capillary format with on-tube detection and automated analysis. Recent advances in the technique provide improved resolution, reproducibility and reliability. This review summarizes improvements in sample preparation, capillary selection, and focusing and zone mobilization procedures which have helped CIEF become a more robust analytical method. New applications are reviewed, in particular the use of CIEF in analysis of biopharmaceutical products.

Electrophoresis, Capillary↗

PubMed1997

Plant polyphenols: biologically active compounds or non-selective binders to protein?

Twenty phenolic compounds, representatives of proanthocyanidins and gallic acid/hexahydroxyldiphenic acid esters of glucose, have been assessed for their ability to inhibit binding of specific radioligands to 16 receptors. The receptors utilized were alpha 1-, alpha 2- and beta-adrenoceptors, adenosine 1, dopamine 1 and 2, muscarinic, Ca2+ channel, sulphonylureas, 5HT1, 5HT1A, 5HT2, histamine 1, benzodiazepine, opiate and Na+/K/ATPase. These phenolic compounds failed to inhibit ligands binding to 10 of the receptors under the test conditions. The most susceptible receptors to phenolic binding were beta-adrenergic, 5HT1 and opiate. Some of the compounds tested showed selectivity for a single or for two receptors. The inhibition of binding of radioligands to receptors by the phenolic compounds cannot be explained solely in terms of phenolic-protein binding. The results indicate that the removal of tannins from plant extracts prior to screening for receptor activities may result in missing biologically active compounds with specificity of action.

Flavonoids↗

PubMed1997

Exercise training in Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus: effects on the B-cell mass, insulin content and fibrosis in the pancreas.

The effects of exercise on alterations in the amount of B-cell mass, insulin content and fibrous tissue present in the pancreas were examined for a diabetic state induced by a 70% pancreatectomy and a prediabetic state in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model for the spontaneous development of non-insulin-dependent diabetes mellitus (NIDDM). The rats (5-weeks old) were trained either by a 6-week running program or sedentary controls, and at 6-weeks of age, received either a 70% pancreatectomy or a sham-pancreatectomy (sham). As in our previous report, persistent hyperglycemia was detected after surgery for both trained pancreatectomized (Px) and sedentary Px groups. In the nondiabetic sham rats, exercise training resulted in a significantly smaller increase in body weight and beneficial effects on the pancreas as reflected by an increase in pancreatic volume, accompanied by increases in B-cell mass and insulin content as well as less connective tissue in the pancreas compared with the sedentary nondiabetic sham rats. The effect was not sufficient to improve sustained hyperglycemia in the trained diabetic Px rats. This is probably due to a decreased capacity for B-cell proliferation in response to an increased demand for insulin. Although exercise failed to improve this inherent defect in B-cell proliferation, it ameliorated the further deterioration of the pancreas which occurred with hyperglycemia, and resulted in a higher quantity of insulin stored per milligram of B-cell mass (as function of B-cell mass) and less fibrosis in the pancreas, compared with the sedentary diabetic Px rats. The findings of the present study suggest that exercise training has a beneficial effect on the pancreas in the nondiabetic state, and also exerts some positive effects in the diabetic state in this model rat.

Animals↗

PubMed1997

Intracellular inhibition of HIV-1 replication using a dual protein- and RNA-based strategy.

Exporting unspliced human immunodeficiency virus type 1 (HIV-1) RNA from the nucleus to the cytoplasm, through an interaction between the viral regulatory Rev protein and Rev response element (RRE) RNA, is a critical step in the HIV-1 life-cycle. Disruption of either Rev or the RRE will completely inhibit HIV-1 replication. As such, a strategy for somatic gene therapy to treat HIV-1 infection by intracellular expression of an anti-HIV-1 Rev single chain variable fragment (SFv) and a ribozyme which specifically targets the RRE was developed. The anti-Rev D8SFv, which specifically targets the Rev activation domain, may be a key component of combination intracellular immunization, as it has been previously shown to potently inhibit Rev function, thereby inhibiting viral replication. In the present studies, different HIV-1 RRE region-specific hammerhead ribozymes were constructed and their anti-HIV-1 replication effects were assayed in diverse RNA polymerase (pol) II and III promoters and vector systems in cell culture. Utilizing this combination of an SFv and a ribozyme as a dual strategy to block HIV-1 replication, both at the protein and RNA level, data from these studies demonstrated that potent inhibition of HIV-1 replication can be achieved via this approach. Combination gene therapies hold promise, analogous to combination chemotherapeutic regimens, for the in vivo treatment of HIV-1 infections.

Base Sequence↗

PubMed1997

The potentiating actions of cigarette smoking on ethanol-induced gastric mucosal damage in rats.

BACKGROUND & AIMS: Cigarette smoking has been associated with peptic ulceration. However, the ulcerogenic mechanisms are still undefined. The aim of this study was to investigate the effects and possible mechanisms of cigarette smoke on ethanol- or cold-restraint stress-induced gastric damage. METHODS: Rats were exposed to cigarette smoke followed by either an ethanol (70%) challenge or cold-restraint stress. The severity of mucosal damage, levels of prostaglandin E2 and leukotriene C4, determined by radioimmunoassay, and neutrophil infiltration in the stomach were assessed. RESULTS: Smoke dose-dependently potentiated ethanol-but not stress-induced ulcer. It reduced mucosal prostaglandin E2 and increased myeloperoxidase activity. Filtered cigarette smoke did not have these effects. The acidic fraction from the filters produced similar potentiating effects and also delayed ulcer healing. Mucosal leukotriene C4 and serum nicotine levels did not correlate with the mucosal injury in the stomach. Neutropenia abolished the ulcerogenic action and the increase of myeloperoxidase activity produced by both cigarette smoke and acidic fraction. CONCLUSIONS: Reduction of prostaglandin E2 and increase in neutrophil accumulation in the gastric mucosa are responsible for the potentiating action of acute smoke exposure on ethanol-induced gastric damage. Substances other than nicotine could contribute to these adverse reactions in the stomach.

Acetic Acid↗

PubMed1997

Effect of human vitreous and hyalocyte-derived factors on vascular endothelial cell growth.

PURPOSE: In the present study we have examined the effects of human vitreous and hyalocyte-conditioned medium on human umbilical vein endothelial cells (HUVEC). METHODS: Human umbilical vein endothelial cells were cultured and treated in quadruplicate with human vitreous and hyalocyte-conditioned medium at different concentrations. Cell numbers were counted on days 1, 3, 5 and 7. Morphological changes and the viability of cells after treatment were also monitored. RESULTS: The results indicate that both human vitreous and hyalocyte-conditioned medium inhibit proliferation and reduce the viability of HUVEC in vitro. These inhibitory effects were dose- and time-dependent. CONCLUSIONS: The observations suggest that human hyalocytes and vitreous contain anti-angiogenic factors that influence vascular endothelial cell-growth. These results, combined with those of previous studies, may yield important information about the functional role of vitreous and hyalocytes in intraocular vascular regression.

Adult↗

PubMed1997

Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1a receptor peptide.

Angiotensin II (ANG II) inhibits delayed rectifier K+ current (IK) and stimulates total Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem, effects mediated via ANG II type 1 (AT1) receptors. Here, we identify potential G protein activator regions of the AT1 receptor responsible for initiating the intracellular changes that lead to alterations in these currents. Intracellular application into cultured neurons of a peptide corresponding to the third cytoplasmic loop of the AT1 receptor (AT1a/i3) mimicked the actions of ANG II on IK and ICa, whereas application of a peptide corresponding to the second cytoplasmic loop (AT1a/i2) did not alter these currents. This modulation of IK and ICa by AT1a/i3 involves intracellular messengers (G alpha q, protein kinase C, and intracellular Ca2+) that are identical to those involved in the modulation of IK and ICa following ANG II activation of AT1 receptors. These data provide functional evidence for a role of the third cytoplasmic loop of the AT1 receptor in G protein coupling and subsequent modulation of ion channel effectors.

Amino Acid Sequence↗

PubMed1997

Functional interactions between neuronal AT1 and AT2 receptors.

Angiotensin II (Ang II), via the activation of the AT1 and AT2 receptors regulates electrophysiological responses of catecholaminergic neurons. This study was designed to determine if functional interactions between AT1 and AT2 receptors exist in a single neuron. Ang II caused two unique electrophysiological responses characteristic of receptor crosstalk. First, Ang II elicited an AT1 receptor-mediated decrease in I(K) followed by an AT2 receptor-mediated increase in I(K). Second, Ang II elicited an AT2 receptor-mediated increase in I(K) followed by an AT1 receptor-mediated decrease in I(K). AT1 and AT2 receptors were co-localized on the catecholaminergic neurons. These observations suggest, for the first time, the existence of a crosstalk between Ang II receptor subtypes that may be significant in the physiological activity of catecholaminergic neurons.

Angiotensin II↗