Search PubMed⌕ Search

Biomedical subjects

M Jung

Publications and source records attributed to M Jung.

At least 73 records · Page 4Linked to original sources
PubMed2000

Mullerian inhibiting substance inhibits breast cancer cell growth through an NFkappa B-mediated pathway.

Müllerian inhibiting substance (MIS), a member of the transforming growth factor-beta superfamily, induces regression of the Müllerian duct in male embryos. In this report, we demonstrate MIS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G(1) phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFkappaB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IkappaBalpha expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFkappaB signaling pathway was required for these processes. These results identify the NFkappaB-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers.

Animals↗
PubMed2000

Farnesyl anthranilate suppresses the growth, in vitro and in vivo, of murine B16 melanomas.

The numbers of isoprene residues and unsaturated bonds, cis/trans configuration, and head group polarity influence the tumor-suppressive potency of acyclic isoprenoid hydrocarbons and alcohols; within the series tested, trans, trans farnesol had the greatest potency. Geraniol esters had increased potency relative to that of the free alcohol. Farnesyl anthranilate induced a concentration-dependent decrease in the B16 melanoma cell population, in part due to an increased proportion of cells in the G1 phase of the cell cycle and in part by the increased the proportion of apoptotic cells. Farnesyl anthranilate (1.5 mmol/kg diet) significantly suppressed the growth of implanted B16 melanomas and lowered the plasma cholesterol levels of tumor-free mice.

Acyclic Monoterpenes↗
PubMed2000

NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin.

Artemisinin and its derivatives, which have been known as antimalarial drugs, have also demonstrated their cytotoxicity against tumor cells. It has been proposed that antitumor activity depends on the lipophilicity of functional group on artemisinin derivatives. Solution structures of two artemisinin derivatives as antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin, were determined by NMR spectroscopy to elucidate structure-activity relationship. According to biological assay, antitumor efficiencies are not dependent upon lipophilicity. Instead, these compounds demonstrated their distinctive structural features of boat/chair conformation and capability to interact with receptors, as they have different efficiencies on antitumor activity. Especially, carboxypropyl moiety or carbonyl moiety in artemisinin derivatives influences the conformation and stability of ring structure. Although the detailed mechanism of antitumor activity by artemisinin derivatives has not been addressed, we suggest that antitumor activity is not determined only with lipophilicity and that artemisinin derivatives have specific target proteins in each type of cancer.

Animals↗
PubMed2000

Asbestos and cigarette smoke cause increased DNA strand breaks and necrosis in bronchiolar epithelial cells in vivo.

Coexposures to asbestos and cigarette smoke cause increased risks of lung cancer in asbestos workers. Although these carcinogens cause DNA damage to epithelial cells in vitro via generation of reactive oxygen species (ROS), it is unclear whether they cause injury to bronchiolar epithelial cells (i.e., the target cells of lung cancers in vivo). We exposed rats to amosite asbestos, cigarette smoke, and the two agents in combination for 1, 2, and 14 d. Numbers of cells exhibiting DNA strand breaks in comparison to sham rats were then evaluated in lungs using the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL) method and by transmission electron microscopy (TEM). Increases in TUNEL-positive, necrotic epithelial cells occurred after exposure to asbestos alone and in an additive fashion after smoke and asbestos in combination. These results indicate that DNA strand breakage and necrosis are prominent mechanisms of injury by asbestos fibers and cigarette smoke in vivo to epithelial cells of the respiratory tract, thus validating in vitro observations from a number of laboratories.

Animals↗
PubMed2000

Constitutive activation of cyclin B1-associated cdc2 kinase overrides p53-mediated G2-M arrest.

Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and that this function is required for the maintenance of genomic integrity. In this study, we investigated a regulatory role of p53 specifically in G2-M transition. Human bladder carcinoma cells lacking functional p53 were synchronized at G1-S, which is preceded by p53-mediated G1 arrest. p53 expression in the synchronized cells was induced by infection with a recombinant adenovirus that encodes p53. After release from the G1-S arrest, the cells progressed to S-phase and G2 but failed to enter mitosis. Biochemical analysis showed that p53 inhibits cell cycle-dependent expression of cdc2 and cyclin B1 and consequently inhibits cdc2 kinase. The role of cyclin B1-associated cdc2 kinase in p53-mediated G2-M arrest was further investigated by expression of both cyclin B1 and cdc2AF, in which inhibitory phosphorylation sites were substituted. The cells expressing both cdc2AF and cyclin B1 showed a constitutive activation of cdc2 kinase during cell cycle progression and passed through G2-M regardless of p53 expression. Therefore, inactivation of cdc2 kinase through cdc2 and cyclin B1 repression is an essential step in p53-mediated G2-M arrest.

CDC2 Protein Kinase↗
PubMed2000

Cytokine profile of liver- and blood-derived nonspecific T cells after liver transplantation: T helper cells type 1/0 lymphokines dominate in recurrent hepatitis C virus infection and rejection.

Orthotopic liver transplantation (OLT) is a successful treatment in patients with hepatitis C virus (HCV)-associated end-stage liver disease worldwide. T lymphocytes and their cytokines are believed to have a pivotal role in the defense against HCV and in allograft rejection. An immunosuppressive drug regimen may cause a cytokine imbalance toward a T helper (TH) cell type 2 profile that is associated with the persistence of infection and acceptance of the graft. The aim of this study is to assess whether cytokine imbalances toward a TH1- or TH2-type response may have a role in recurrent HCV infection and rejection after OLT. Twenty-one intrahepatic T-cell lines of 15 patients with recurrent HCV infection after OLT (group A) and 15 lines of 11 patients with rejection (group B) were studied. Both patient groups had received liver allografts because of HCV-associated end-stage liver disease. Patients with HCV-induced liver disease who did not undergo OLT served as controls: 17 patients with chronic hepatitis C (CH-C) and 8 patients with cirrhosis. At the time of liver biopsy, 14 blood-derived T-cell lines of 12 patients with recurrent HCV infection, 7 of 10 patients with rejection, and 18 of 18 control patients were also investigated. Regardless of the underlying disease (recurrent HCV infection, rejection, HCV-induced hepatitis, and cirrhosis), all liver tissue-derived T-cell lines produced interferon-gamma; some additionally produced interleukin-4 (IL-4), but none produced IL-10, indicating that the TH0/1 cytokine profile dominates. T-cell lines showing a TH1 cytokine profile derived from intrahepatic T cells could be established significantly more often in recurrent HCV infection and rejection than in controls with CH-C (Fisher's exact test, P <.05). The cytokine profile of intrahepatic T cells did not differ from that obtained in peripheral blood. TH0/1 cytokine profile dominates the intrahepatic and blood-derived immune response in recurrent HCV infection and rejection after OLT regardless of the mode of immunosuppression. The lymphokine profile of immunocompromised patients with recurrent HCV infection or rejection does not differ principally from that of patients with HCV-induced hepatitis and cirrhosis, but seems to show a TH1 profile significantly more often.

Cytokines↗
PubMed2000

Lesion-induced regulation of netrin receptors and modification of netrin-1 expression in the retina of fish and grafted rats.

To determine whether netrin receptors (DCC, UNC5H1, UNC5H2) and netrin-1 are present in the adult rat retina and may affect regeneration of retinal ganglion cell (RGC) axons into peripheral nerve (PN) grafts, in situ hybridization (ISH) and immunostaining experiments were performed in normal and operated rats. Netrin-1 expression was not found in the optic nerve head of adult rats, normal and postlesion, but appeared transiently at 7 and 14 days after PN grafting. ISH signals of netrin receptors, however, disappeared from RGCs within 2 days after lesion and remained absent after PN grafting except for UNC5H2, which transiently occurred in a few RGCs. Netrin-1 expression was observed in the optic nerve head of adult fish, normal and postlesion, and the netrin-1 Fc fusion protein bound to young growing and all regenerating axons. Thus, the netrin-1-dependent guidance system continues to function in fish but apparently no longer operates in adult rats.

Animals↗
PubMed2000

Genetics of atopy in a mouse model: polymorphism of the IL-5 receptor alpha chain.

To study the genetics of atopy systematically we established a mouse model that provides the general phenotype of atopy: the early response characteristic of IgE-dependent eczema or atopic dermatitis, and the diagnostic test of atopy, the skin-prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains respectively as high responder and low responders. The F1 hybrids were found to be high responders with incomplete penetrance. Backcrossing F1 mice to the low responder B6 strain yielded three classes of responders, high, intermediate, and low. A genome-wide microsatellite screen of the backcross progeny disclosed suggestive linkage to a microsatellite marker on chromosome 6 close to the locus of the IL-5 receptor alpha chain. Its allelic variation in A/J and B6 strains was investigated and two major differences were detected. Firstly, a nucleotide exchange in the 5' untranslated region of B6 mRNA resulted in increased transcription/translation of a reporter construct. Higher expression of the receptor on the cell surface would be expected to favor an allergic immune response. Secondly, the two alleles are differentially spliced so as to yield two soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble IL-5R would be expected to reduce the level of allergy through capture of IL-5. Thus both findings conform to the expectation based on susceptibility to atopy and thus identify the IL-5R alpha chain as a likely contributor to the genetics of atopy.

Alternative Splicing↗
PubMed2000

Using acoustic emission signals for monitoring of production processes.

The systems for in-process quality assurance offer the possibility of estimating the workpiece quality during machining. Especially for finishing processes like grinding or turning of hardened steels, it is important to control the process continuously in order to avoid rejects and refinishing. This paper describes the use of on-line monitoring systems with process-integrated measurement of acoustic emission to evaluate hard turning and grinding processes. The correlation between acoustic emission signals and subsurface integrity is determined to analyse the progression of the processes and the workpiece quality.

Acoustics↗
PubMed2000

Effects of hepatocellular iron imbalance on nitric oxide and reactive oxygen intermediates production in a model of sepsis.

BACKGROUND/AIMS: In mammals iron homeostasis is most important, as imbalance of iron such as iron overload may lead to severe diseases. Recently, it has been shown that the iron regulatory protein-1 is partially controlled by nitric oxide and reactive oxygen intermediates, molecules frequently seen in inflammatory events. The aim of the present study was to investigate the effects of impaired iron homeostasis on the interaction of nitric oxide, and reactive oxygen intermediate formation in hepatocytes in a model of acute inflammation. METHODS: Hepatocytes isolated from Corynebacterium parvum (C parvum)-injected rats were used to examine the formation of nitrogen and oxygen intermediates by iron deprivation and iron overload in the presence of lipopolysaccharide. In addition, we investigated the RNA binding and aconitase activity of iron regulatory protein-1. RESULTS: In the present study we show that iron overload in lipopolysaccharide-treated C. parvum-primed hepatocytes downregulated the RNA binding of iron regulatory protein-1 and aconitase activity. Subsequently, we observed a reduced formation of nitrite/nitrate and S-nitrosothiols but an increased production of reactive oxygen species, and hepatocellular damage. Moreover, the addition of iron to cell cultures caused a further increase in cellular damage, a drop in the cellular glutathione pool, and an increase in peroxynitrite and hydroxyl-like radicals. In contrast, addition of deferoxamine (an iron chelator) to lipopolysaccharide-treated C. parvum-primed hepatocytes protected cells by stabilizing the GSH content, maintaining the nitric oxide formation, and by reducing Fenton oxidants. CONCLUSIONS: Our results show that the antioxidative effects of iron chelators prevent the formation of toxic Fenton oxidants in severe inflammatory events, which should be considered in the treatment of disorders characterized by an iron imbalance.

Animals↗
PubMed2000

[ESES-syndrome in child- and adolescent psychiatry].

OBJECTIVES: The article describes the theoretical background of the diagnosis and therapy of the ESES syndrome. METHODS: The assessment and treatment of children with ESES in a child-psychiatric setting is shown. The underlying data have been taken from 18 outpatients with or without epileptic seizures. RESULTS: The early diagnosis of non-specific symptoms and the anti-epileptic treatment probably play an important role in preventing the progression of ultrastructural brain damage. Sultiam is the drug of first preference.

Anti-Anxiety Agents↗
PubMed2000

Genome-wide, large-scale production of mutant mice by ENU mutagenesis.

In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

Animals↗
PubMed2000

Fas ligand gene-carrying adeno-5 AdEasy viruses can be efficiently propagated in apoptosis-sensitive human embryonic retinoblast 911 cells.

Recent reports have pointed out the difficulties in generating recombinant adenoviral vectors expressing FasL using eukaryotic cells. In the present study we cloned the murine FasL (mFasL) gene into the pCA14 or pShuttle vectors and recombined them with the adeno-5 virus backbone pBHG10 or pAdEasy-1 in eukaryotic (911 cells) or prokaryotic (E. coli) cells, respectively. Recombination of pCA14-mFasL with pBHG10 in Fas-carrying 911 cells leads to rapid expression of mFasL and cell death by apoptosis before virus replication is initiated. The same effect is observed when 911 cells are transfected with the pCA14-mFasL shuttle vector only. If recombination (pShuttle-mFasL with pAdEasy-1) is performed first in bacteria and 911 cells are transfected thereafter with recombined AdEasy-mFasL, virus production starts immediately and the cells survive longer. The resulting AdEasy-mFasL viruses are able to infect other eukaryotic cells and induce expression of functional mFasL. This study describes a method for efficient generation of recombinant FasL adeno-5 viruses in eukaryotic cells. The method may be generally suitable for producing viruses carrying deleterious genes. Gene Therapy (2000) 7, 70-74.

Adenoviridae↗
PubMed2000

The Burch-Schneider antiprotrusio cage in acetabular revision surgery: a mean follow-up of 12 years.

A total of 38 acetabular revisions using a Burch-Schneider antiprotrusio cage in 37 patients (18 women and 19 men), with a mean age at surgery of 75 years (range, 55-88 years), were evaluated retrospectively with a mean follow-up of 12 years (range, 8-21 years). In 2 cases with total hip dislocation and in 1 case with a deep infection, revision of the antiprotrusio cages was required. Defining every revision of the antiprotrusio cage as the endpoint of survivorship, the antiprotrusio cage showed a survival rate of 92% after 21 years. Clinical evaluation of the surviving patients showed a mean Harris hip score of 76 points (range, 20-96). Radiologic evaluation revealed that 1 antiprotrusio cage was loose and that 4 femoral stems were loose. The Burch-Schneider antiprotrusio cage compares favorably with other devices with regard to long-term implant survival rate.

Aged↗
PubMed2000

Improved sedation in diagnostic and therapeutic ERCP: propofol is an alternative to midazolam.

BACKGROUND AND STUDY AIMS: Adequate sedation of the patient is required for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). The anesthetic propofol, with its shorter half-life, affording better control, offers an alternative to the benzodiazepine midazolam. The aim of this randomized, controlled, unblinded study was to compare prospectively the quality of sedation under propofol and midazolam in patients undergoing ERCP. PATIENTS AND METHODS: A total of 80 patients were randomized to sedation with propofol alone (n = 40) or midazolam alone (n = 40). Blood pressure, pulse, and oxygen saturation were measured. Midazolam was given by the endoscopist and titrated to the patients' response during ERCP, to a maximum dose of 15 mg per patient. In the propofol group an anesthetist was present to administer the propofol and to observe the patient. Standardized testing procedures (Steward score, Trieger test) were used to determine the length of postendoscopy recovery time. Efficacy of sedation was assessed by investigators and patients, using scoring systems. RESULTS: Complete ERCP and adequate sedation was possible in 80% of patients (32 out of 40) with midazolam, and in 97.5% of patients (39 out of 40) with propofol (P<0.01). The average propofol induction dose was 1.24 mg/kg body weight, with maintenance requiring a mean dose of 9 mg/kg body weight per hour, or the equivalent of 354 mg in total. The average dose of midazolam administered was 0.12 mg/kg body weight; the total dose averaged 8 mg. Recovery time in the propofol patients was significantly shorter (P<0.01). The investigators (P<0.01) and the patients (P<0.05) both judged the quality of sedation to be better in the propofol group. There were no differences in blood pressure, pulse, or oxygen saturation between the two groups. One patient in the propofol group (79 years old) suffered a protracted apneic phase accompanied by hypotension that was managed by manual ventilation and drug therapy, and led to no complications. CONCLUSIONS: Propofol proves to be an excellent sedative for ERCP and shows a shorter recovery time than midazolam. Because of the narrow therapeutic window, we recommend close patient monitoring.

Anesthesia Recovery Period↗