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  • 1
    Electronic Resource
    Electronic Resource
    THE MUTAGENIC EFFECT OF D2O ON BACTERIOPHAGE T4 (1960)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 84 (1960), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1960.tb39100.x
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  • 2
    Electronic Resource
    Electronic Resource
    Applications of Genetic Engineering to the Pharmaceutical Industry (1983)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 413 (1983), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1983.tb47874.x
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  • 3
    Electronic Resource
    Electronic Resource
    Phase I study of cancer therapy with recombinant interleukin-2 administered by intravenous bolus injection (1989)
    Springer
    Biotherapy 1 (1989), S. 215-226 
    Details
    ISSN: 1573-8280
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixty-six patients with disseminated malignancy were treated with recombinant interleukin-2 (IL-2) on a three times a week (M, W, F) IV-bolus injection schedule. Doses ranged from 0.001 to 14.0 × 106 units/M2 body surface area. Consecutive groups of 3-5 patients were placed on each dose level and were maintained on that level except for dosage de-escalation for toxicity. Toxicity to all major organ systems were noted with major toxicity including fever and chills, anorexia, fatigue and malaise, arthralgias and arthritis as well as hepatic and renal toxicity. All toxicity reversed within one week of drug cessation. Renal toxicity manifested by azotemia, arthritis and fatigue were the common dose limiting toxicities and the maximally tolerated dose was 12 × 106 units/M2. Pharmacokinetic studies indicated a short half-life (T 1/2α = 7–23 minutes). At doses over 0.5 × 106 units/M2 increases in absolute lymphocytes and eosinophil counts were noted. All T lymphocyte subsets increased. Maximal increases were seen at 4–8 × 106 units/M2 with a lesser increase at 10–14 × 106 units/M2 dosage level. Circulating NK cells also increased while circulating LAK cells were detected during therapy. Partial responses were noted in 3 patients with melanoma. These lasted 4, 6 and 16 months and involved pulmonary, pulmonary plus mesenteric and retro-orbital plus hepatic metastases respectively in these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02170890
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  • 4
    Electronic Resource
    Electronic Resource
    Transfer distribution of the DNA of T4 phage over its progeny (1965)
    Springer
    Molecular genetics and genomics 96 (1965), S. 66-82 
    Details
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The distribution of the DNA of bacteriophage T4 over progeny produced by an infection ofE. coli with32P-labeled, deuterated parent phages was ascertained by examining the density of the transferred DNA in intact progeny virus particles and in DNA molecules extracted from progeny or phage-infected cells. The following results were obtained: 1. Those progeny phage that contain the bulk of transferred parental32P derive approximately 10% of their DNA from the parent. This value is a weight average, but it can be estimated that most of the transferred parental32P appears in progeny whose DNA complement comprises no less than 7 and no more than 13% atoms of parental origin. 2. In control experiments involving non-deuterated T4 parent phage, the transferred parental DNA appears in phage particles that are less dense than the average progeny. This fact must be taken into account in the interpretation of transfer distribution experiments involving density labels. 3. After breakage of the progeny DNA molecule into small fragments less than 1% of its original size, all the transferred parental atoms are found to reside in fragments that contain 50% parental atoms. This result is consistent with the interpretation that these fragments are half parental — half newly synthesized hybrid DNA molecules generated by semi-conservative replication. 4. The fragmentation of the parental DNA molecule occurs early in the infective process, no later than the start of replication of the vegetative phage DNA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00897236
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  • 5
    Electronic Resource
    Electronic Resource
    Expression of a β-Lactamase Preproinsulin Fusion Protein in Escherichia Coli (1984)
    [s.l.] : Nature Publishing Company
    Nature biotechnology 2 (1984), S. 165-168 
    Details
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] The level of expression of a β-lactamase human preproinsulin fusion protein1 in Escherichia coli was increased by plasmid and host manipulations. The initial expression level (0.01% of total protein) was increased two- to three-fold by replacing the p-lactamase promoter with two strong ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nbt0284-165
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  • 6
    Electronic Resource
    Electronic Resource
    Assessment of the antigenic response in humans to a recombinant mutant interferon beta (1987)
    Springer
    Journal of clinical immunology 7 (1987), S. 365-375 
    Details
    ISSN: 1573-2592
    Keywords: Interferon ; recombinant ; cancer ; immunogenicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cancer patients were given a recombinant mutant interferon β by alternating IM and IV injections with weekly escalation of doses from 0.1 to 400 million U. Antibodies specific to the interferon of the IgG class were detected in 24 of 30 patients using an indirect enzyme-linked immunosorbent assay. Serum from only 1 of the 30 patients had detectable ability to neutralize interferon biological activity. Thein vivo interferon serum level, assayed as antiviral activity immediately after IV injection, was not lower than levels seen in the absence of antibodies. Antibodies did not alter the kinetics of clearance of interferon from the serum after IV administration. Antibody levels progressively decreased when interferon administration was discontinued. In most patients antibody levels decreased during a maintenance period when interferon was being administered only by the IV route. In a subsequent trial interferon was given IV, and antibody developed in only 2 of 36 patients. In contrast, in a trial in which interferon was given IM, 20 of 25 patients developed antibody. No antibody-related clinical sequelae could be detected in any of these patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00917014
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  • 7
    Electronic Resource
    Electronic Resource
    The development of anti-interleukin-2 antibodies in patients treated with recombinant human interleukin-2 (IL-2) (1986)
    Springer
    Journal of clinical immunology 6 (1986), S. 481-490 
    Details
    ISSN: 1573-2592
    Keywords: Interleukin-2 ; antibodies ; lymphokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Approximately 65% (11/17) of cancer patients participating in an ongoing Phase I clinical trial with recombinant interleukin-2 developed nonneutralizing serum IgG anti-interleukin-2 antibodies within 1 month of initiating therapy. These antibodies could be detected using any of several standard techniques including immunoblots and enzyme-linked immunosorbent assays. Western blot analysis and retention experiments with protein A-Sepharose indicate that the antibodies are specific for interleukin-2. The interleukin-2 mutein utilized in this clinical trial (des-ala-ser125 r-IL-2) differs from the major species of the human T cell-derived lymphokine in that it lacks the N-terminal alanine of the native molecule, is not glycosylated, and possesses a serine-cysteine substitution at position 125. Another recombinant interleukin-2, identical to the mutein except that it retains the cysteine at position 125 (des-ala-cys125 r-IL-2), strongly competes with the mutein in competitive enzyme-linked immunosorbent assays, suggesting that the amino acid substitution is not responsible for the recognition of the molecule by serum antibodies. Conversely, nonrecombinant T cell-derived interleukin-2 fails to compete in these assays and is not retained by protein A-Sepharose columns when mixed with high-titer antiserum. These results suggest that the anti-interleukin-2 serum antibodies generated in the course of treatment do not react with the nonrecombinant lymphokine but recognize epitopes peculiar to recombinant forms which are not dependent on the amino acid substitution at position 125. The failure of the antibodies to neutralize the biological activity of recombinant interleukin-2 (IL-2) in lymphocyte proliferation assays and to bind to the native lymphokine suggests that they may not affect IL-2-dependent cellular immune functionsin vivo.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00915254
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  • 8
    Electronic Resource
    Electronic Resource
    A phase I trial of intraperitoneal recombinant interleukin 2 in patients with ovarian carcinoma (1988)
    Springer
    Investigational new drugs 6 (1988), S. 179-188 
    Details
    ISSN: 1573-0646
    Keywords: intraperitoneal interleukin 2 ; ovarian carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Seven patients with refractory stage III ovarian carcinoma were treated with escalating doses of human recombinant interleukin 2 (rIL-2) administered via the intraperitoneal (IP) route in an attempt to establish a dose and schedule of rIL-2 suitable for prolonged outpatient IP administration. Three patients went on to receive outpatient maintenance treatment twice weekly for 2–3 months. Doses ranged from 105 to 5 × 107 U/m2. The dose found most suitable for twice weekly outpatient IP administration was 106 U/m2. Dose-limiting toxicities consisted of diarrhea resulting in hypovolemia (5 patients) fever and chills (4 patients), nausea and vomiting (1 patient), mental status changes (2 patients), and azotemia (1 patient). These side effects were not prevented by indomethacin. Significant hypotension was not observed. Pharmacokinetic studies revealed extremely high IP concentrations of IL-2 which persisted for more than 24 hours. After a dose of 106 U/m2, the IP concentrations ranged from 670 to 760 U/ml. In one patient in whom concurrent serum concentrations were determined, the IP concentrations were over 100-fold higher than serum levels. After a dose of 107 U/m2, the IP concentrations of IL-2 ranged from 8700 to 14000. Concurrent serum levels in one patient revealed IP concentrations over 500-fold higher than serum levels. There were no consistent changes in T cell surface and activation markers on mononuclear cells from peripheral blood in 3 patients tested. Natural killer cell (NK) activity in peripheral blood increased in the three patients in whom it was measured. Four of the 7 patients progressed on treatment; 3 patients remained stable. We conclude that 106 U/m2 of rIL-2 is well-tolerated when administered by the IP route and that concentrations of IL-2 well in excess of that required to enhance cell-mediated cytotoxicity in vitro persist in the IP fluid for at least 24 hours.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175395
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  • 9
    Electronic Resource
    Electronic Resource
    Stimulation of RNA chain initiation by the N gene protein of bacteriophage λ (1974)
    Springer
    Molecular genetics and genomics 134 (1974), S. 359-366 
    Details
    ISSN: 1617-4623
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary RNA transcription from the early leftward operon of the bacteriophage λ was studied. Hybridization to the separated DNA strands of the wild type phage, and to a biotin transducing phage containing viral sequences of only the extreme right or promoter proximal segment of this operon, allowed measurement of the rate of RNA chain initiation with respect to the total amount of RNA transcribed from this operon. Procedures which reduced either the amount of N gene protein synthesized, or its activity, were seen to depress transcription from the promoter proximal region approximately as much as from the entire operon. The RNA made when transcription was depressed did not have a conspiciously lower molecular weight, and the DNA-polymerase-RNA complex contained a correspondingly reduced number of polymerase molecules. All these observations are consistent with, and suggest, that under these conditions the function of the protein specified by gene N is to increase the frequency of initiation of RNA chains.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00337470
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  • 10
    Electronic Resource
    Electronic Resource
    Untersuchungen zur Chemie von Isoindolen und Isoindoleninen, XXVIII. 3-Alkoxy-1H-isoindole  -  Synthesen und Eigenschaften (1988)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 121 (1988), S. 243-252 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Studies on the Chemistry of Isoindoles and Isoindolenines, XXVIII.  -  3-Alkoxy-1H-isoindoles, Syntheses and Properties3-Alkoxy-1H-isoindoles 1 bearing substituents at the carbocyclic moiety have been synthesized from substituted 2,3-dihydro-1H-isoindol-1-ones 4 by regiospecific O-alkylation to 5 with trialkyloxonium tetrafluoroborates or methyl trifluoromethanesulfonate and subsequent NH deprotonation. According to the spectroscopic properties the semicyclic alkyl imidates 1 exist exclusively in the benzenoid 1H structure; the tautomeric o-quinonoid 2H structure 2 cannot be detected by spectroscopic means.
    Notes: 3-Alkoxy-1H-isoindole 1 mit Substituenten am carbocyclischen Teil wurden aus substituierten 2,3-Dihydro-1H-isoindol-1-onen 4 durch regiospezifische O-Alkylierung mit Trialkyloxonium-tetrafluoroboraten oder Trifluormethansulfonsäure-methylester zu 5 und nachfolgende NH-Deprotonierung synthetisiert. Aufgrund der spektroskopischen Befunde existieren die semicyclischen Imidsäure-alkylester 1 ausschließlich in der benzoiden 1H-Form; die tautomere 2H-Form 2 mit o-chinoider Struktur ist spektroskopisch nicht nachweisbar.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19881210209
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