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Biomedical subjects

M Lipp

Publications and source records attributed to M Lipp.

At least 73 records · Page 4Linked to original sources
PubMed1995

Akv murine leukemia virus enhances lymphomagenesis in myc-kappa transgenic and in wild-type mice.

The contribution of endogenous retroviruses to the multistep process of lymphomagenesis was investigated in wild-type mice and in two different myc-kappa transgenic mouse lines by infection with Akv. This retrovirus is derived from the endogenous ecotropic provirus of the AKR mouse and was previously considered to be nonlymphomagenic. The mice of the two myc-k transgenic lines are predisposed to B-cell lymphomagenesis and were therefore considered to be more susceptible to Akv. For comparison, the same mouse strains were also infected with the exogenous Moloney murine leukemia virus (MoMuLV). Both MoMuLV and Akv increased the tumor incidence and shortened the tumor latency period in wild-type mice and in the transgenic mouse lines. The differences in pathogenicity, number of provirus integrations, and level of virus expression between MoMuLV and Akv indicate different mechanisms of lymphomagenesis: while MoMuLV induced tumors apparently by insertional mutagenesis involving common integration sites similar to previous reports, the enhancement of lymphomagenesis by Akv seems to be directed by other mechanisms.

AKR murine leukemia virus↗
PubMed1995

[Analgesia-sedation for maxillo-facial surgery with midazolam-pentazocine and miazolam-ketamine. Clinical double-blind study of anxiety, analgesia, sedation and amnesia].

UNLABELLED: Ketamine and midazolam, applied as intravenous medication for conscious sedation in day-case maxillo-facial surgery, has been proven to be superior to pentazocine and midazolam concerning cardiovascular parameters and respiratory depression. The aim of this study was to evaluate the effects of low-dose ketamine/midazolam on anxiety, analgesia, amnesia and subjective feelings. METHODS. 140 out-patients (ASA I) were randomly divided into four groups. The double-blind study was prospective. CONTROL GROUP: Local anaesthesia (LA), articaine 4% plus epinephrine 1:200,000 (n = 35); test group P/M: LA, additional pentazocine 0.40 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35); test group K25/M: LA, additionally ketamine 0.25 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35), test group K50/M: LA, additionally ketamine 0.5 mg/kg bw and midazolam 0.075 mg/kg bw i.v. (n = 35). LA was injected 3 min after application of the systemic medication in the test groups or application of a placebo (saline 0.9%) in the control group. Three further minutes later, operation was started. For evaluation questionnaires, visual analogue scales (VAS) and the state-trait anxiety inventory (STAI) were used. For testing retrograde and anterograde amnesia, acoustic sensations were delivered before application of the systemic medication (a Christmas carol) and during operation (the German national anthem). RESULTS. The control group and the test groups were comparable with regard to biological data, duration of operation, applied dosage of local anaesthetics and actual anxiety before operation. The patients in all test groups rated intraoperative anxiety as mild, in contrast to the control group. Nearly no pain sensation during the operation was remembered in all test groups. Retrograde amnesia was not found in any group. Complete anterograde amnesia was observed in all test groups with respect to the intraoperative sensation, but even in the control group 50% of the patients did not remember having heard the national anthem. As subjective feelings negative criteria were mainly reported in the control group, where as in all test groups positive sensations dominated. Dreams were reported mostly after the higher dosage of ketamine, but no patient experienced any unpleasant dreams. The clinical assessment of the different regimes were excellent for test groups P/M and K50/M, modest for the control group and test group K25/M. Postoperatively, patients of test group P/M were remarkably sedated, but no clinically relevant sedation or motor weakness were observed in the other groups. Postoperative pain sensations were rated more intense in all test groups than in the control group. In test groups P/M and K25/M an increasing pain level was recorded during the postoperative period, with the consequence of a higher demand rate for analgesics. CONCLUSIONS. Dental surgery can be performed safely with low-dose ketamine/midazolam. Compared to pentazocine/midazolam, the higher dosage of ketamine (0.5 mg/kg bw) showed identical results intraoperatively, but was superior during the postoperative period (vigilance), and thus may represent a suitable dosage. The lower dosage of ketamine resulted in worse operating conditions, but a dosage higher than 0.5 mg/kg bw might lead to unconscious sedation and might increase the frequency of unpleasant dreams.

Adjuvants, Anesthesia↗
PubMed1995

Sulfated polysaccharide anticoagulants suppress natural killer cell activity in vitro.

In contrast to the well studied anticoagulant activity of sulfated polysaccharides (SPS), little is known about their influence on immune competent cells. Using two naturally derived SPSs (unfractionated heparin and low molecular weight heparin), one semi-synthetic SPS (pentosanpolysulfate), and one synthetic SPS (lactobionic acid) as well as the polypeptide hirudin we investigated the effect of these drugs on natural killer cell activity in vitro. We demonstrate that all SPSs tested significantly suppress the activity of natural killer cells at clinically relevant dosages. At all concentrations and at all effector:target ratios tested pentosanpolysulfate was the most potent natural killer cell inhibitor. In contrast, hirudin had no effect on natural killer cell function. Furthermore, scanning electron microscopy revealed that reduced natural killer cell activity is paralleled by decreased lymphocyte cell size and altered cell surface structures. Our results indicate that defined therapeutically applied SPSs can interfere with the tumor cell killing process.

Anticoagulants↗
PubMed1994

Expression of the G-protein--coupled receptor BLR1 defines mature, recirculating B cells and a subset of T-helper memory cells.

The G-protein-coupled receptor BLR1 related to receptors for chemokines and neuropeptides has been identified as the first lymphocyte-specific member of the gene family characterized by seven transmembrane-spanning regions. Using a high-affinity anti-BLR1 monoclonal antibody (MoAb) and three-color flow cytometry it is shown that BLR1 expression on peripheral blood cells is limited to B cells and to a subset of CD4+ (14%) and CD8+ (2%) lymphocytes. T cells expressing BLR1 were positive for CD45R0, were negative for interleukin-2 receptors, show high levels of CD44, and show low levels of L-selectin. The majority of CD4+ cells originating from secondary lymphatic tissue, but none of cord blood-derived T cells, express BLR1. These observations suggest that BLR1 is a marker for memory T cells. Furthermore, BLR1 expression was detected on all CD19+ peripheral or tonsillar B lymphocytes, but only on a fraction of cord blood cells and bone marrow cells expressing CD19, sIgM, or sIgD. Interestingly, activation of both mature B and T cells by CD40 MoAb and CD3 MoAb, respectively, led to complete downregulation of BLR1. These data suggest that the G-protein-coupled receptor BLR1 is involved in functional control of mature recirculating B cells and T-helper memory cells participating in cell migration and cell activation.

Adult↗
PubMed1994

Cloning and chromosomal organization of a gene encoding a putative amino-acid permease from Saccharomyces cerevisiae.

A new member of the yeast amino acid (aa) permease gene family has been cloned, mapped and sequenced. The sequence of the PAP1 (putative aa permease 1) gene contains an open reading frame of 566 aa corresponding to a polypeptide with a calculated M(r) of 62,704. Its hydropathy profile suggests the presence of 13 membrane-spanning regions and a charged N-terminal domain. It does not resemble hydrophobic signal sequences found in secreted proteins. Hence, PAP1 encodes a protein with characteristics typical of integral membrane proteins translocating ligands across cellular membranes. Sequence comparisons indicate strong homology to the five known aa permeases of Saccharomyces cerevisiae and to an aa transporter in Trichoderma harzianum. Primer extension analysis revealed one major and one minor transcription start point located 121 and 125 nucleotides upstream from the ATG start codon, corresponding to a 2.1-kb transcript. PAP1 was mapped in a contig of three known (DBF4, TPI and HEM12), but so far unlinked, genes on chromosome IV.

Amino Acid Sequence↗
PubMed1994

Activation of a tumor-associated protein kinase (p40TAK) and casein kinase 2 in human squamous cell carcinomas and adenocarcinomas of the lung.

Several non-small cell lung carcinomas (squamous cell carcinomas and adenocarcinomas) were analyzed for protein kinase activity. Soluble protein extracts derived from these tumors and from the lung parenchyma adjacent to the tumors were resolved by Mono Q anion exchange chromatography, and the fractions were assayed for phosphotransferase activity towards in vitro substrates. Myelin basic protein, casein, and a ribosomal S6-1 COOH-terminus peptide were efficient substrates for protein kinases that exhibited elevated phosphotransferase activity in the tumor extracts when compared to extracts derived from the adjacent nonneoplastic lung or from the lung parenchyma from patients with nonneoplastic lung disorders. Casein phosphotransferase activity was resolved into two peaks that eluted at 0.44 M NaCl and 0.56 M NaCl. The second peak was identified as casein kinase 2, based upon immunoreactivity to casein kinase 2-specific antipeptide antibodies and its sensitivity to inhibition by heparin sulfate. Myelin basic protein phosphotransferase activity eluted at 0.44 M NaCl, but Western blot analysis revealed that this could not be ascribed to mitogen-activated protein (MAP) kinases. This tumor associated protein kinase, designated p40TAK, exhibited a molecular mass of approximately 40 kDa upon gel filtration. In addition to myelin basic protein, it phosphorylated S6 peptide analogues and histone H1 on seryl residues. Like casein kinase 2, p40TAK exhibited elevated basal phosphotransferase activity in squamous cell carcinomas and adenocarcinomas of the lung when compared to the nonneoplastic lung parenchyma adjacent to the tumor.

Adenocarcinoma↗
PubMed1994

Breakpoints of Burkitt's lymphoma t(8;22) translocations map within a distance of 300 kb downstream of MYC.

The variant translocation t(8;22) in Burkitt's lymphoma (BL) cells joins band q24 of chromosome 8 distal to the proto-oncogene MYC to the immunoglobulin lambda locus. The distribution of breakpoints on chromosome 8 of 11 cell lines with t(8;22) has been investigated by in situ fluorescence hybridization and pulsed-field gel electrophoresis. We show that these chromosomal breakpoints generally fall within a region of about 300 kb 3' of MYC and that at least 8 out of 11 affect the previously characterized transcriptional unit PVT1. Comparable results were obtained in earlier experiments analyzing the variant t(2;8). Recently, in a series of BL cells carrying t(8;14), breakpoints upstream of MYC have been described at a similar distance. Therefore, our results suggest that deregulation of MYC by the immunoglobulin loci can occur at a distance of up to about 350 kbp of MYC.

Burkitt Lymphoma↗
PubMed1994

[Analysis of requests for help. Emergency calls to the fire department and emergency medical services, as well as to the general medical practitioners' emergency services in a rescue service area].

There is no doubt that a single emergency phone number is desirable, but in contrast to other countries, in Germany different emergency phone numbers and dispatching centers exist for the fire brigade (FB), the emergency medical service system (EMS), and the general practitioners' emergency service (GPS). Due to this fact, valuable time is often wasted by connecting or transferring emergency calls from one dispatching center to another. The purpose of this study was to analyse all calls received by the different dispatching centers in the city and county area of Mainz with respect to total number, fraction of emergency calls, and specificity. Further, the total number of calls potentially referring to a hypothetic single dispatching center with a general emergency phone number (112) was calculated. During a 4-month period, all telephone calls were registered and related to day, time, and origin of the call (city or county) and classified as non-urgent or emergency calls, calls appropriate to the dispatching center dialed, emergency calls to be transferred, or unspecific calls. A total of 80,987 calls were received (city area 84.3%, county area 15.7%), most of them directed to the FB of Mainz (33,086). The EMS dispatching center received 31,286 calls, the five GPS-centers 15,256 calls; 1359 emergency calls that were directed to the police or FB needed transfer to the EMS. During weekdays the EMS and FB received the most calls, with a reduced frequency on Saturdays and Sundays (Table 2). Nevertheless, the highest total numbers of calls were received on Saturdays due to multiple calls directed to the GPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergency Medical Service Communication Systems↗
PubMed1994

Selective expression of the murine homologue of the G-protein-coupled receptor BLR1 in B cell differentiation, B cell neoplasia and defined areas of the cerebellum.

The Burkitt's lymphoma receptor 1 (BLR1) identified initially in Burkitt lymphoma cells has been the first member of the superfamily of G-protein-coupled receptors with a lymphocyte specific expression pattern. BLR1 shows significant relationship to receptors for chemokines (IL-8, MIP-1 beta) and neuropeptides. The gene encoding the murine homologue of the human BLR1 receptor was isolated and used to study its tissue-specific expression. Blr-1 consists of two exons encoding a protein of 374 amino acid residues which shows 83% identity with the human homologue. Screening of normal tissues of adult BALB/c mice revealed that blr-1-specific RNA is detected consistently at low levels in secondary lymphatic organs. The blr-1 gene is expressed regularly and strongly in lymphomas of mature B cells but not in plasmacytomas. SCID mice deficient in the development of mature B cells have strongly reduced levels of blr-1-specific RNA in the spleen. Cytokine mediated induction (IL4, IL6) of terminal differentiation of resting B cells towards Ig-secreting plasma cells completely downregulates expression of blr-1. RNA in situ hybridization using brain sections demonstrates blr 1 transcription in the granule and Purkinje cell layer of the cerebellum. The precise delineation of the restricted expression pattern of the blr-1 gene will support the identification of its ligand and may provide a clue to understand how BLR1 exerts its biological function within the immune and nervous system.

Amino Acid Sequence↗
PubMed1994

Transmembrane topology of the lymphocyte-specific G-protein-coupled receptor BLR1: analysis by flow cytometry and immunocytochemistry.

The blr1 gene encodes the first member of the superfamily of G-protein-coupled receptors showing a lymphocyte- and differentiation-specific expression pattern. To study the synthesis of the BLR1-protein and to characterize the receptor we fused its coding region to a sequence derived from human c-MYC allowing the detection of the corresponding fusion protein by an anti-myc-antibody. Expression of the epitope-tagged BLR1 in human embryonic kidney 293 cells to high levels showed an apparent molecular mass for BLR1 of 50 kDa. This is reduced to 40 kDa following treatment of the cells with tunicamycin indicating the presence of N-linked glycosylation. Furthermore expression of amino- and carboxyl-terminally tagged BLR1 demonstrated that BLR1 is an integral protein of the plasma membrane inserted therein in the predicted orientation. Using this efficient expression system we generated a monoclonal antibody (mAb 8B2) against human BLR1. Flow cytometric analysis of peripheral blood lymphocytes confirms the lymphocyte-specific expression of BLR1. The highly efficient expression of BLR1 in 293 cells and the generated mAb offers a powerful tool for further characterization of this receptor and analysis of its function on lymphocytes and during B-cell development.

Amino Acid Sequence↗
PubMed1994

Transcriptional repression and activation in the same cell type of the human c-MYC promoter by the retinoblastoma gene protein: antagonisation of both effects by SV40 T antigen.

The c-myc promoter was investigated as a possible cellular target for SV40 large T (LT) antigen. In fibroblast and epithelial cell lines, the human c-myc promoter was transactivated by LT. This transactivation was dependent of the interaction of LT with the retinoblastoma (RB) protein. The use of deletions and point mutations of the c-myc promoter demonstrated that in both cell types, the E2F binding sites are necessary for such transactivation. Unexpectedly however, over-expression of RB caused an overall transcriptional activation of the c-myc promoter. We resolved this apparent paradox by demonstrating that this activation is a combination of two antagonistic effects: transcriptional repression mediated by the E2F factor, and transcriptional activation independent of this factor. RB was also found to prevent LT-mediated transactivation, and LT inhibited RB-mediated activation independently of the E2F factor. LT therefore antagonizes both the transcriptional repression and activation mediated by RB.

Animals↗
PubMed1994

Computerised dynamic posturography: its place in the evaluation of patients with dizziness and imbalance.

As well as vestibular information, computerised dynamic posturography (CDP) measures visual and proprioceptive contributions to the balance system. Three hundred and seventy-five patients were evaluated by computerised dynamic posturography and the results were compared to electronystagmography (ENG) results. CDP demonstrated abnormalities in the balance system in many of the patients who had normal ENGs. It can hone the physician's skill in recognising subtle balance disease; it does not provide localization to one side; it does not offer disease-specific information; however, taken in conjunction with history, physical examination, and other tests, CDP will prove to be a helpful addition to the battery of tests available, and it may provide an objective measure of abnormal balance function in contentious cases.

Adult↗
PubMed1994

E2F-dependent regulation of human MYC: trans-activation by cyclins D1 and A overrides tumour suppressor protein functions.

Transcription of the human proto-oncogene MYC is repressed in quiescent or non-dividing cells. Upon mitogenic stimulation expression of MYC is rapidly and transiently induced, maintained throughout G1, and declines to a basal level throughout further cell cycle transitions. Regulation of MYC promoter activity critically depends on the presence of a binding site for transcription factor E2F. Human E2F has been implicated also in the control of cell cycle progression through it association with the retinoblastoma suppressor gene product RB, and with multimeric protein complexes containing the G1-S- and S-phase cyclins E and A, respectively. Using CAT reporter co-transfection assays we show here that transcription from the MYC P2 promoter is induced efficiently by E2F-1, but repressed by RB. Furthermore, overexpression of cyclin A strongly activates the MYC promoter and this effect is further enhanced by coexpression of E2F-1 and cyclin A. We also find that expression of G1-phase cyclin D1 leads to an E2F binding site-dependent trans-activation of the MYC promoter and that this activation can be abrogated by overexpression of RB. The interaction of D-type G1 cyclins with RB resembles that of the adenovirus E1A protein with RB in that it can disrupt inhibitory E2F-RB complexes. Our results support a model in which intervention of distinct cyclins and their respective associated kinases promotes transcriptional activation of MYC throughout the cell cycle either by conversion of E2F within multimeric complexes into an active transcription factor or by liberation of free functional E2F.

Base Sequence↗
PubMed1994

The hepatitis B virus preS2/St transactivator utilizes AP-1 and other transcription factors for transactivation.

Integrated hepatitis B virus DNA cloned from hepatitis B virus-associated hepatocellular carcinoma frequently contains 3'-truncated middle surface genes (preS2/St), which were recently found to have a transcriptional transactivator function. Because preS2/St, among others, is able to transactivate the promoters of the cellular oncogenes c-myc and c-fos, it has been speculated that integrated preS2/St genes might contribute to hepatitis B virus-associated liver carcinogenesis. In this study, we investigated the mechanism of target gene stimulation by preS2/St. It was found that deletion of a fragment containing the binding site for transcription factor AP-1 (Jun-Fos) substantially decreases inducibility of the human c-myc promoter by preS2/St. A subsequent investigation of AP-1 activation by preS2/St revealed the following: (a) insertion of multimeric AP-1 binding sites confers inducibility to an otherwise unstimulatable test promoter; (b) transactivation of AP-1 sites is dramatically increased when Jun and Fos are overexpressed by cotransfected expression plasmids; and (c) inhibitors of AP-1 activation also impair transactivation by preS2/St. Besides AP-1, preS2/St was also able to utilize the unrelated transcription factors NF-kappa B and AP-2 for transactivation, suggesting that the gene product of preS2/St acts indirectly through one or several general cellular pathways rather than as a bona fide transcription factor. Because AP-1 conveys induction of a large panel of tumor-relevant genes, its preS2/St-dependent activation implies a possible causative role in hepatitis B virus-associated hepatocarcinogenesis.

Animals↗
PubMed1993

Topological characterization of the lymphoid-specific seven transmembrane receptor BLR1 by epitope-tagging and high level expression.

We have tagged the human lymphocyte-specific G-protein-coupled receptor BLR1 either with an amino-terminal or a carboxyl-terminal epitope-tag recognized by an anti-MYC monoclonal antibody. Flow cytometry was used to determine the efficiency of transient transfections and to establish human embryonic kidney 293 cell clones showing stable high level expression of BLR1. Analysis of permeabilized versus non-permeabilized transfected 293 cells demonstrated that BLR1 is an integral plasma membrane protein, topologically oriented therein as predicted for other members of this class of seven pass membrane receptors. In addition, BLR1 was expressed in 293 cells to high levels as a glycosylated membrane protein. The easily detectable and assayable expression of tagged G-protein-coupled receptors, as exemplified for BLR1 in 293 cells, provides a suitable system for further functional studies and offers an efficient screening tool for the identification of receptor-specific antibodies, ligands, or receptor-associated proteins.

Amino Acid Sequence↗
PubMed1993

A general method for screening mAbs specific for G-protein coupled receptors as exemplified by using epitope tagged BLR1-transfected 293 cells and solid-phase cell ELISA.

Monoclonal antibodies (mAb) against G-protein coupled receptors are rare. In this study we describe a cell ELISA-based screening system for monoclonal antibodies specific for the G-protein coupled receptor BLR1 (Eur. J. Immunol. 1992. 22:2795) using human embryonic kidney 293 cells transfected with a modified human BLR1 cDNA directing the synthesis of an epitope tagged BLR1 protein. Lou/C rats were immunized with BLR1 transfected, tagged 293 cells and after fusion of spleen cells with X63 Ag8.653 myeloma cells supernatants were tested for BLR1 specific antibodies by comparing the binding to BLR1 transfected 293 cells and to untransfected control cells immobilised on poly-L-lysine coated microtiter plates. Cells were fixed with 2% paraformaldehyde and permeabilized using digitonin in order to allow binding of mAb directed against intracellular epitopes. This mild fixation retained excellent morphology of 293 cells and allowed reliable binding to the trays. Screening of approximately 2500 supernatants identified 19 antibodies binding to BLR1 transfected 293 cells but not to control 293 cells. One of these mAb specifically bound to the G-protein coupled receptor BLR1.

Animals↗
PubMed1993

Identification of a protein from Saccharomyces cerevisiae with E2F-like DNA-binding and transactivating properties.

The promoter of the human proto-oncogene MYC has been the first cellular target shown to be subject to regulation by the E2F transcription factor. E2F also has binding sites in other promoters regulated by cell proliferation and during the cell cycle. We have analyzed Saccharomyces cerevisiae for the presence of an E2F-analogous protein. GAL1-based promoter constructs carrying the E2F binding site of the MYC or the adenovirus E2 promoter showed transcriptional activity in yeast cells. A DNA-binding factor, designated YE2F, binds specifically to the E2F consensus sequence and was partially purified from yeast extracts. YE2F showed identical contact points within the MYC binding site as authentic E2F protein from mammalian cells. The results suggest that the existence of an E2F-like protein in the yeast S. cerevisiae.

Amino Acid Sequence↗