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Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

At least 595 records · Page 33Linked to original sources
PubMed1995

Detection of hepatitis C virus RNA in the cell fraction of saliva before and after oral surgery.

The presence of hepatitis C virus (HCV) RNA in serum, whole saliva, and saliva from the submaxillary glands was investigated before and after oral surgery. The presence of HCV RNA (positive and negative-strand RNA) was determined in serum and saliva by a nested polymerase chain reaction in 26 anti-HCV positive patients, of whom 11 were coinfected with human immunodeficiency virus-1. Oral surgery was carried out on five occasions on four of the patients. HCV RNA was detected in the sera of 23 of 26 (88%) patients, and in the saliva of 4 of the 23 (17%) of the viremic patients. In all four cases, HCV RNA was detected only in the cell fraction derived from centrifugation of whole saliva. Negative-stranded HCV RNA was not detected. At one of five occasions of oral surgery, HCV RNA was detected in saliva sampled immediately after surgery, but not before or 24 hours after surgery. The results suggest that HCV is present in saliva in less than 25% of HCV viremic persons. The presence of the virus in saliva is restricted to the cell fraction. Thus, saliva may serve as a possible, but low, nonparenteral transmission route of HCV. Contamination of saliva by blood during and after oral surgery may result in an increased risk of viral exposure. Except for trauma caused by sharp instruments during surgery, this might contribute to the higher HCV seropositivity found among dentists.

Dentists↗
PubMed1995

Anti-tumor effects and tumor immunogenicity following IL2 or IL4 cytokine gene transfection of three mouse mammary tumors.

BACKGROUND: The anti-tumor effects of three mouse mammary tumors transfected to express interleukin (IL) 2 or 4 were evaluated. METHODS: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected using high efficiency viral vectors. Wild-type or transfected tumor cells were injected subcutaneously into Balb/c mice and animals were observed for tumor growth. RESULTS: Overall, there was a significant decrease in the incidence and in the size of palpable transfected tumor compared with control tumors. Animals were immunized with wild-type or transfected cells and challenged with wild-type tumor. In these experiments, animals immunized with transfected tumor cells had a significantly lower incidence of tumor and significantly smaller tumors than controls. Similar experiments were performed by immunization with irradiated cells (wild type and transfected), and significant immune protection was induced. CONCLUSIONS: Each cell line responded differently following gene transfection, with the greatest anti-tumor effects seen in the EMT6 tumor cells transfected with IL2 or IL4.

Animals↗
PubMed1995

Antitumor activity of three mouse mammary cancer cell lines after interferon-gamma gene transfection.

BACKGROUND: The antitumor effects of three mouse mammary tumors transfected to express interferon-gamma were evaluated. METHODS: Three immunologically different tumors were used: DA3, EMT6, and 410. All three cell lines were successfully transfected with highly efficient viral vectors. Wild type or transfected tumor cells were injected subcutaneously into Balb/c mice. Animals were observed for tumor growth and the induction of immunologic memory. RESULTS: A significant decrease occurred in the size of all transfected tumors, EMT6 1.9 cm2, DA3 1.7, and 410 1.8 compared with nontransfected control tumors with a mean size of 4 cm2 on day 30. To further test the development of immunity, animals were injected with either nontransfected or transfected tumors and challenged with nontransfected tumor. Animals immunized with transfected tumor cells had significantly smaller tumors, EMT6 2.5 cm2, DA3 3.1, and 410 2.4 compared with controls with a mean size of 4 cm2. No specific splenocyte cytotoxicity was shown. Expression of major histocompatibility complex class I antigens was enhanced in the 410 and DA3 tumor lines. CONCLUSIONS: Significant antitumor effects were observed after interferon-gamma gene transfection of three mouse mammary cancer cell lines. Up-regulation of major histocompatibility complex class I antigen expression is a partial explanation of these findings. These results provide preliminary studies for gene therapy of human breast cancer.

Animals↗
PubMed1995

Somatic mutations in the BRCA1 gene in sporadic ovarian tumours.

The BRCA1 gene on chromosome 17q21 is responsible for an autosomal dominant syndrome of increased susceptibility to breast and ovarian cancer but no somatic mutations in tumours have yet been described. To study the potential role of BRCA1 in sporadic carcinogenesis, we analysed the genomic DNA of tumour and normal fractions of 47 ovarian cancers for mutations in BRCA1 using the single-strand conformation polymorphism technique. We now describe somatic mutations in the DNA of four tumours which also had loss of heterozygosity (LOH) at a BRCA1 intragenic marker. Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers.

Adolescent↗
PubMed1995

Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide.

Paired helical filament (PHF) tau is the principal component of neurofibrillary tangles, a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD). Post-translational modification of tau, especially phosphorylation, has been considered a major factor in aggregation and diminished microtubule interactions of PHF-tau. Recently, it has been recognized that PHF-tau is also subject to non-enzymatic glycation, with formation of advanced glycation end products (AGEs). We now show that as a consequence of glycation, PHF-tau from AD and AGE-tau generate oxygen free radicals, thereby activating transcription via nuclear factor-kappa B, increasing amyloid beta-protein precursor and release of approximately 4 kD amyloid beta-peptides. These data provide insight into how PHF-tau disturbs neuronal function, and add to a growing body of evidence that oxidant stress contributes to the pathogenesis of AD.

Alzheimer Disease↗
PubMed1995

Distinguishing acute from symptomatic chronic hepatitis C virus (HCV) infection by site-directed serology of the HCV structural proteins.

To distinguish acute from symptomatic chronic hepatitis C virus (HCV) infection, site-directed serology was done on the complete core, envelope 1, and envelope 2 proteins using multiple peptide assays. Serum samples were obtained from 7 patients with clinically confirmed acute HCV infections and from 36 patients with symptomatic chronic HCV infections. At onset of symptoms, all patients with acute infection had HCV RNA in serum, 1 had > 2 strong core peptide reactivities (A405 > 1.0), and the number of core reactivities increased with time in 6 patients. In contrast, 35 of 36 chronic-phase patients with HCV RNA in serum had 3-12 strong core reactivities (P < .001). Envelope 2 antibodies were found in 2 acute-phase and in 32 chronic-phase HCV patients (P < .01). Thus, a serum sample with HCV RNA from a patient with hepatitis can be classified as acute or chronic using site-directed serology of the HCV structural proteins.

Acute Disease↗
PubMed1995

Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions.

Vitronectin (Vn) is a multifunctional plasma and extracellular matrix glycoprotein involved in cell attachment, coagulation, phagocytosis, and the protection of bystander cells from complement- and T cell-mediated lysis. To determine where Vn is localized and where cells expressing integrin Vn receptors may recognize it in central nervous system (CNS) lesions of multiple sclerosis (MS), CNS tissue samples were immunostained for Vn and the alphav, beta 1, and beta 3 integrin Vn receptor subunits. By light and electron microscopy, Vn was localized within dystrophic, demyelinated axons in active but not chronic lesions, normal or other neurologic disease controls. This localization is distinct from that of other plasma proteins in MS lesions and it differs from the pattern of neuron cell body localization found in other conditions. Microvascular Vn was increased and small numbers of reactive astrocytes were also Vn-positive in active plaques. Endothelial cell expression of the alpha v subunit was increased over controls and that of the beta 1 subunit was decreased whereas both the alpha v and beta 1 subunits were prominently expressed on macrophages and glia in active lesions. The beta 3 integrin subunit was expressed on platelets within and around vessels and was more prominent on endothelial cells in active plaques. The precise functions of Vn in situ are not presently known. These results indicate, however, that the regulation of expression of integrin Vn receptors is complex and that Vn may be recognized and have multiple functions in different microanatomic sites as MS lesions evolve. Intravascular Vn could participate in clotting, thereby contributing to leukocyte extravasation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

The antileishmanial agent licochalcone A interferes with the function of parasite mitochondria.

Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial (M. Chen, S.B. Christensen, J. Blom, E. Lemmich, L. Nadelmann, K. Fich, T.G. Theander, and A. Kharazmi, Antimicrob, Agents Chemother. 37:2550-2556, 1993; M. Chen, S.B. Christensen, T.G. Theander, and A. Khrazmi, Antimicrob. Agents Chemother. 38:1339-1344, 1994) and antimalarial (M. Chen, T.G. Theander, S.B. Christensen, L. Hviid, L. Zhai, and A. Kaharazmi, Antimicrob. Agents Chemother. 38:1470-1475, 1994) activities. We have observed that licochalcone A alters the ultrastructure of the mitochondria of Leishmania promastigotes (Chen et al., Antimicrob. Agents Chemother. 37:2550-2556, 1993). The present study was designed to examine this observation further and investigate the mechanism of action of antileishmanial activity of licochalcone A. Electron microscopic studies showed that licochalcone A altered the ultrastructure of Leishmania major promastigote and amastigote mitochondria in a concentration-dependent manner without damaging the organelles of macrophages or the phagocytic function of these cells. Studies on the function of the parasite mitochondria showed that licochalcone A inhibited the respiration of the parasite by the parasites. Moreover, licochalcone A inhibited the activity of the parasite mitochondrial dehydrogenase. The inhibition of the activity of the parasite mitochondrial enzyme correlated well with the changes in the ultrastructure of the mitochondria shown by electron microscopy. These findings demonstrate that licochalcone A alters the ultrastructure and function of the mitochondria of Leishmania parasites.

Animals↗
PubMed1995

DNA polymerase beta can substitute for DNA polymerase I in the initiation of plasmid DNA replication.

We previously demonstrated that mammalian DNA polymerase beta can substitute for DNA polymerase I of Escherichia coli in DNA replication and in base excision repair. We have now obtained genetic evidence suggesting that DNA polymerase beta can substitute for E. coli DNA polymerase I in the initiation of replication of a plasmid containing a pMB1 origin of DNA replication. Specifically, we demonstrate that a plasmid with a pMB1 origin of replication can be maintained in an E. coli polA mutant in the presence of mammalian DNA polymerase beta. Our results suggest that mammalian DNA polymerase beta can substitute for E. coli DNA polymerase I by initiating DNA replication of this plasmid from the 3' OH terminus of the RNA-DNA hybrid at the origin of replication.

Ampicillin Resistance↗
PubMed1995

Levels of hepatitis C virus (HCV) RNA in serum and their relationship to levels of immunoglobulin M and G antibodies against HCV core protein.

The presence and levels of hepatitis C virus (HCV) RNA and immunoglobulin M (IgM) and IgG antibodies against the virus core protein were determined in 449 serum specimens. Despite the fact that a relationship between the presence, but not the levels, of HCV RNA and HCV IgM was observed, the significance of HCV core IgM assays seems limited.

Biomarkers↗
PubMed1995

Ser-3 is important for regulating Mos interaction with and stimulation of mitogen-activated protein kinase kinase.

Mos is a germ cell-specific serine/threonine protein kinase that activates mitogen-activated protein kinase (MAPK) through MAPK kinase (MKK). In Xenopus oocytes, Mos synthesis is required for progesterone-induced activation of MAPK and maturation promoting factor. Injection of Mos or active MAPK causes mitotic arrest in early embryos, suggesting that Mos also acts via MKK and MAPK to induce the arrest of unfertilized eggs in metaphase of meiosis II. We have investigated whether Mos activity is regulated by phosphorylation. Previous studies have identified Ser-3 as the principal autophosphorylation site. We show that Mos interacts with the catalytic domain of MKK in a Saccharomyces cerevisiae two-hybrid test. Acidic substitutions of the sites phosphorylated by Mos in MKK reduce the interaction, implying that the complex may dissociate after phosphorylation of MKK by Mos. Furthermore, the Mos-MKK interaction requires Mos kinase activity, suggesting that Mos autophosphorylation may be involved in the interaction. Substitution of Ser-3 of Mos with Ala reduces the interaction with MKK and also reduces both the activation of MKK by Mos in vitro and cleavage arrest induced by Mos fusion protein in Xenopus embryos. By contrast, substitution of Ser-3 by Glu, an acidic amino acid that mimics phosphoserine, fosters the Mos interaction with MKK and permits activation of MKK in vitro and Mos-induced cleavage arrest. Moreover, the Glu-3 substitution increases the interaction of a kinase-inactive Mos mutant with MKK. Taken together, these results suggest that an important step in Mos activation involves the phosphorylation at Ser-3, which promotes Mos interaction with and activation of MKK.

Animals↗
PubMed1995

Effects of Ca2+ ionophore ionomycin on insulin-stimulated and basal glucose transport in muscle.

There is evidence that an increase in sarcoplasmic Ca2+ stimulates glucose transport in muscle. Recent studies have provided the apparently conflicting finding that a sustained increase in cytosolic Ca2+ has little effect on basal glucose transport but inhibits insulin-stimulated transport. This study was done to try to explain this discrepancy. Continuous exposure of rat epitrochlearis and soleus muscles to the Ca2+ ionophore ionomycin (2 microM) had no effect on basal 2-deoxyglucose (2-DG) transport but blunted, by approximately 40%, stimulation of 2-DG transport by insulin. Decreasing Ca2+ in the medium to a very low level prevented this inhibition. Ionomycin induced a small increase in adenosine 3',5'-cyclic monophosphate (cAMP); however, studies with the protein kinase A (PKA) inhibitor HA-1004 provided evidence that activation of PKA by cAMP does not mediate the inhibition of glucose transport. When muscles were allowed to recover in the absence of ionomycin for 15 min, basal 2-DG transport was significantly increased. Our results agree with previous studies showing that a sustained influx of Ca2+ into the cytoplasm can inhibit insulin-stimulated glucose transport. They further show that stimulation of glucose transport by Ca2+ is also inhibited. A recovery period that allows this inhibition to wear off unmasks the stimulation of glucose transport by an increase in sarcoplasmic Ca2+.

Animals↗
PubMed1995

Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.

Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.

Anesthetics, Inhalation↗
PubMed1995

Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi OspA or B.

The evolution of Lyme borreliosis in transgenic mice tolerant to Borrelia burgdorferi outer surface proteins (Osps) A or B was assessed to investigate the role of immunity to OspA or B in infection and pathogenesis of Lyme disease. Antibodies to OspA or B protect immunocompetent C3H/HeJ or C.B.17 severe combined immunodeficient (scid) mice from challenge with B. burgdorferi. Moreover, arthritis in infected C3H mice resolves with the rise of high titers of B. burgdorferi specific antibodies, including OspA and B, whereas disease persists in scid mice--suggesting that the regression of arthritis may be due to the development of borreliacidal OspA or B antibodies. To evaluate the course of Lyme borreliosis in OspA or B tolerant mice we developed transgenic mice that expressed OspA or B under control of the major histocompatibility complex (MHC) class I promoter. Mice carrying OspA or B transgenes on a C3H/HeJ (C3H, disease-susceptible) or C57BL/6 (B6, disease-resistant) background, immunized with OspA or B, did not mount a humoral or cellular immune response to OspA or B, respectively, but responded normally to other B. burgdorferi antigens. The evolution of Lyme borreliosis, including infection and the development of arthritis and carditis, was similar in transgenic and nontransgenic littermates suggesting that an OspA or B immune response is not singularly involved in either the genesis or regression of Lyme disease in C3H or B6 mice.

Animals↗
PubMed1995

[Determination of modulus of elasticity of human periodontal membrane].

The modulus of elasticity of periodontal membrane, as an essential parameter indicating the mechanical character of periodontal membrane, is very important in biomechanical studies (e.g. finite element stress analysis and photoelastic analysis) of dental restoration. However, determination of modulus of elasticity of human periodontal membrane has not been reported in China, and there are differences among the foreign reports. In this study, 135 periodontal samples were collected from fresh teeth and alveoli of 6 healthy adults. Drawing and compressing test were performed. The results showed that the tensile modulus of elasticity of human periodontal membrane is between 3.35 and 4.59MPa and the compress modulus of elasticity 0.5402(+/- 0.348) MPa.

Adult↗