A new antitumor antibiotic, fredericamycin A (FCRC-A48, NSC-305263), has been isolated from a strain of Streptomyces griseus .Based on its unique ultraviolet-visible spectrum, infrared spectrum, proton and carbon-13 nuclear magnetic resonance spectra and mass spectra, it is judged to be a novel acid-base indicator type of compound.Its production, isolation and physicochemical properties are discussed. The isolation, ultraviolet-visible spectrum and some biological properties of two minor components, fredericamycin B and fredericamycin C, are also described.During the course of a screening program for new antitumor antibiotics, we isolated a strain of Streptomyces griseus (FCRC-48) from a soil sample in Frederick, Maryland. Fermentation broths of S. griseus (FCRC-48) repeatedly showed high in vitro activity against KB and P388 tumor cell lines and in vivo activity against P388 tumor cells. A complex of several biologically active compounds was isolated from acidified (pH 2.0) filtered broth by cooling to 4°C for 96 hours or by extraction with ethyl acetate. Purification of the complex resulted in the isolation of one major and two minor components.Other components were present, but were not isolated. This paper deals with the production, isolation and physicochemical characterization of fredericamycin A (FCRC-A48, NSC-305263), the major component. The ultraviolet-visible spectrum and some biological properties of the two minor components fredericamycin B and fredericamycin C are also reported. The biological properties of fredericamycin A are presented in the accompanying publication'). Materials and Methods GeneralMelting points, determined on a Koller micro hot stage apparatus, are uncorrected. Ultravioletvisible (UV-VIS) spectra were taken in methanol on a GCA/McPherson ultraviolet-visible spectrophotometer, Model EU-700-32. Infrared (IR) spectra (micro KBr pellet) were run by Mr. N. RISSER on a Perkin Elmer spectrophotometer, Model 180. Proton nuclear magnetic resonance (1H NMR) spectra were determined on a Varian HR-220 spectrometer equipped with a Nicolet Instrument Corp. TT220 Fourier transform accessory. Carbon-13 nuclear magnetic resonance (1IC NMR) spectra were run on a JEOL FX60 spectrometer. The electron impact mass spectra (EIMS) were run by Mr. S. HUANG on a Finnigan 3300 GC/MS with a 6000 MS data system at 70 eV (solid probe). Field desorption (FD) mass spectra were measured by Dr. G. MCCLUSKY on a Vg Micromass ZAB-2F mass spectrometer, equipped with a combination electron impact (El)-chemical ionization (CI)-field ionization (FI)-FD ion source
ABSTRACT. We investigated the association between the interleukin 4 gene (IL-4) -590C>T polymorphism and forced expiratory volume in one second (FEV 1 ) values, immunoglobulin E (IgE) levels, and susceptibility to asthma in Uighur children. IL-4 -590C>T frequencies were analyzed in 38 bronchial asthmatic patients and 35 non-asthmatic controls. Polymerase chain reaction and direct sequencing were applied to determine the residue at position -590 of IL-4. Total serum IgE levels were detected by enzyme-linked immunosorbent assay, while lung function was examined by professionals. There were significant differences in the distribution of IL-4 -590C>T genotypes and alleles between patient and control groups (genotypes: chi-square = 11.476, P < 0.05; alleles: chi-square = 14.572, P < 0.05). Frequencies of CC, CT, and TT genotypes were 21, 29, and 50% among patients, and 49, 37, and 14% among controls, respectively, indicating that the T allele was significantly more frequent in the asthma group than in the control group. Total serum IgE levels were significantly higher (P < 0.05) and FEV 1 values were significantly lower (F = 13.294, P < 0.05) in patients than in control subjects of the same genotype. In conclusion, the IL-4 -590C>T polymorphism is related to bronchial asthma in Uighur children, and the T allele may constitute a susceptibility factor in this group. Furthermore, this genetic variant can result in raised IgE levels and decreased FEV 1 values, suggesting that both factors are associated with bronchial asthma in Uighur children.
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