Showing papers by "Novartis published in 1990"

MacroModel—an integrated software system for modeling organic and bioorganic molecules using molecular mechanics

Abstract: An integrated molecular modeling system for designing and studying organic and bioorganic molecules and their molecular complexes using molecular mechanics is described. The graphically controlled, atom-based system allows the construction, display and manipulation of molecules and complexes having as many as 10,000 atoms and provides interactive, state-of-the-art molecular mechanics on any subset of up to 1,000 atoms. The system semiautomates the graphical construction and analysis of complex structures ranging from polycyclic organic molecules to biopolymers to mixed molecular complexes. We have placed emphasis on providing effective searches of conformational space by a number of different methods and on highly optimized molecular mechanics energy calculations using widely used force fields which are supplied as external files. Little experience is required to operate the system effectively and even novices can use it to carry out sophisticated modeling operations. The software has been designed to run on Digital Equipment Corporation VAX computers interfaced to a variety of graphics devices ranging from inexpensive monochrome terminals to the sophisticated graphics displays of the Evans & Sutherland PS300 series.

Miniaturized total chemical analysis systems: A novel concept for chemical sensing

Abstract: Following the trend towards smaller channel inner diameter for better separation performance and shorter channel length for shorter transport time, a modular construction of a miniaturized 'total chemical analysis system' is proposed. The theoretical performances of such systems based on flow injection analysis, chromatography and electrophoresis, are compared with those of existing chemical sensors and analysis systems.

Gene Transfer into Humans — Immunotherapy of Patients with Advanced Melanoma, Using Tumor-Infiltrating Lymphocytes Modified by Retroviral Gene Transduction

Abstract: Background and Methods. Treatment with tumor-infiltrating lymphocytes (TIL) plus interleukin-2 can mediate the regression of metastatic melanoma in approximately half of patients. To optimize this treatment approach and define the in vivo distribution and survival of TIL, we used retroviral-mediated gene transduction to introduce the gene coding for resistance to neomycin into human TIL before their infusion into patients — thus using the new gene as a marker for the infused cells. Results. Five patients received the gene-modified TIL. All the patients tolerated the treatment well, and no side effects due to the gene transduction were noted. The presence and expression of the neomycin-resistance gene were demonstrated in TIL from all the patients with Southern blot analysis and enzymatic assay for the neomycin phosphotransferase coded by the bacterial gene. Cells from four of the five patients grew successfully in high concentrations of G418, a neomycin analogue otherwise toxic to eukaryotic cell...

Illustration of Bayesian Inference in Normal Data Models Using Gibbs Sampling

Abstract: The use of the Gibbs sampler as a method for calculating Bayesian marginal posterior and predictive densities is reviewed and illustrated with a range of normal data models, including variance components, unordered and ordered means, hierarchical growth curves, and missing data in a crossover trial. In all cases the approach is straightforward to specify distributionally and to implement computationally, with output readily adapted for required inference summaries.

Increase in Salicylic Acid at the Onset of Systemic Acquired Resistance in Cucumber

Abstract: In an effort to identify the signal compound that mediates systemic acquired resistance (SAR), changes in the content of phloem sap were monitored in cucumber plants inoculated with either tobacco necrosis virus or the fungal pathogen Colletotrichum lagenarium. The concentration of a fluorescent metabolite was observed to increase transiently after inoculation, with a peak reached before SAR was detected. The compound was purified and identified by gas chromatography-mass spectrometry as salicylic acid, a known exogenous inducer of resistance. The data suggest that salicylic acid could function as the endogenous signal in the transmission of SAR in cucumber.

Nomenclature for the major histocompatibility complexes of different species: a proposal

Abstract: The major histocompatibility complex (MHC) has been given different names in different species (Klein 1986). It is designatedH-2 in the mouse, HLA in humans, B in the domestic fowl, RT1 in the rat, and Smh in the mole rat. In most other species that have been studied, the MHC is referred to by the LA symbol (for lymphocyte or leukocyte antigen), prefixed by an abbreviation of the species’ common name. Thus, it is called ChLa in the chimpanzee, GoLA in the gorilla, RhLA in the rhesus macaque, RLA in the rabbit, BoLA in the domestic cattle, SLA in the pig, and so on. This practice has two problems associated with it. First, MHC products are expressed on many other tissues in addition to lymphocyte or leukocyte (and lymphocytes express many other antigens in addition to those controlled by the MHC) and their antigenicity is secondary to their biological function. Second, the use of common names to identify a species is a potential source of confusion. Common names are notoriously vague and imprecise. The designation “lemur”, for example, can refer to any of the genera Lemur, Hapalemur, Varecia, Lepilemur; Avahi, Propithecus, and Indri, of which only the first four belong to the family Lemuridae; the last three are members of the family Indriidae. A “bushbaby” can be a Galago, Otolemur, or Euoticus. A “mouse” could be a Notomys, ylcomys, Uranomys, Pogomys, Chiruromys, Chiropodomys, Neohydromys, and so on. Obviously, common names not only fail to identify the species appropriately, they often do not even identify the genes or the family. If the trend in choosing common names for MHC symbols were to continue, chaos would soon ensue because we can expect MHCs in many different species to be identified in the future.

Detection and Typing of Human Papillomavirus in Archival Cervical Cancer Specimens by DNA Amplification With Consensus Primers

Abstract: We developed a polymerase chain reaction DNA amplification system using two distinct consensus oligonucleotide primer sets for the improved detection and typing of a broad spectrum of human genital papillomavirus (HPV) sequences, including those of novel viruses. The system incorporates one primer set designed to amplify a highly conserved L1 domain and a second primer set designed to amplify a domain within the E6 gene. We used this system to analyze 48 fixed, paraffin-embedded tissue sections (41 specimens from 33 cervical carcinomas, four normal cervical tissues, and several control tissues) for the presence of HPV DNA. HPV sequences were detected in all carcinoma samples and none of the control samples. Hybridization analyses showed that the results obtained with the two amplification schemes concurred completely. This approach allowed rapid confirmation of typing results and may improve the likelihood of detecting a wide variety of HPV sequences, including those of novel HPVs.

Detection of Somatostatin Receptors in Surgical and Percutaneous Needle Biopsy Samples of Carcinoids and Islet Cell Carcinomas

Abstract: Somatostatin (SS) receptor status was investigated in the tumor tissues from 62 patients with carcinoid tumors and 15 patients with islet cell carcinomas using receptor autoradiography techniques with two different iodinated somatostatin analogues as radioligands, a [Leu8, DTrp22, Tyr25]somatostatin-28 and a somatostatin octapeptide, Tyr3-octreotide. The carcinoid tumors were either primaries (n = 32) or metastases (n = 43), sampled as surgical specimens or as small needle liver biopsies. Fifty-four of 62 carcinoid patients had SS receptor-positive tumors (87%). All 15 islet cell carcinoma patients had positive tumors (4 primaries, 11 metastases), i.e., 3 vipomas, 3 insulinomas, 2 glucagonomas, 1 gastrinoma, 2 polyfunctional tumors, and 4 nonfunctioning tumors. Saturation and competition experiments on tissue sections revealed saturable, high affinity binding sites pharmacologically specific for bioactive SS analogues. In a majority of the tumors, the receptors were densely distributed and were always homogeneously found in the whole tumor. All except two tumors were labeled with both radioligands. Multiple liver metastases (n = 16) from three different patients were all shown to contain a comparable amount of receptors. SS receptors could be demonstrated even in very small tissue samples of liver metastases obtained by percutaneous liver biopsies (mean weight, 6.8 mg). The majority of the eight SS receptor-negative carcinoids were mainly bronchial carcinoids (n = 5), usually poorly differentiated. On the contrary, SS receptor-positive cases were never found to be anaplastic. All tumors except one from patients pretreated with octreotide (3 days to 3.8 years) were SS receptor positive. In the majority of carcinoids or islet cell carcinomas, the SS receptor status correlated with the in vivo biochemical response (hormone inhibition) to octreotide. These data demonstrate (a) the high prevalence of SS receptors in the primary tumors of both carcinoids and islet cell carcinomas, (b) their presence in metastases as well, (c) their continuous expression even during long term octreotide therapy, (d) the possibility of measuring SS receptors in percutaneous needle liver biopsies, and (e) the evidence of their functionality. This study therefore suggests that tumoral SS receptors may be the likely molecular basis for octreotide action and may be an important parameter for predicting the therapeutic efficacy of SS analogues in carcinoids and islet cell carcinomas.

Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition.

Abstract: Thrombin is a serine protease that plays a central role in blood coagulation It is inhibited by hirudin, a polypeptide of 65 amino acids, through the formation of a tight, noncovalent complex Tetragonal crystals of the complex formed between human alpha-thrombin and recombinant hirudin (variant 1) have been grown and the crystal structure of this complex has been determined to a resolution of 295 A This structure shows that hirudin inhibits thrombin by a previously unobserved mechanism In contrast to other inhibitors of serine proteases, the specificity of hirudin is not due to interaction with the primary specificity pocket of thrombin, but rather through binding at sites both close to and distant from the active site The carboxyl tail of hirudin (residues 48-65) wraps around thrombin along the putative fibrinogen secondary binding site This long groove extends from the active site cleft and is flanked by the thrombin loops 35-39 and 70-80 Hirudin makes a number of ionic and hydrophobic interactions with thrombin in this area Furthermore hirudin binds with its N-terminal three residues Val, Val, Tyr to the thrombin active site cleft Val1 occupies the position P2 and Tyr3 approximately the position P3 of the synthetic inhibitor D-Phe-Pro-ArgCH2Cl Thus the hirudin polypeptide chain runs in a direction opposite to that expected for fibrinogen and that observed for the substrate-like inhibitor D-Phe-Pro-ArgCH2Cl

Increased Secretion of Tumor Necrosis Factor α, Interleukin 1, and Interleukin 6 by Human Mononuclear Cells Exposed to β-Galactoside-specific Lectin from Clinically Applied Mistletoe Extract

Abstract: A β-galactoside-specific lectin from proprietary mistletoe extract, recently reported to exhibit immunomodulatory potency in vivo (T. Hajto, K. Hostanska, and H-J. Gabius, Cancer Res. 49: 4803–4808, 1989), induced increased secretion of tumor necrosis factor α, interleukin 1, and interleukin 6 in cultures of human peripheral blood mononuclear cells. The enhancement of secretion, determined independently by bioassays and enzyme-linked immunosorbent assay-based quantitation, was caused by selective protein-carbohydrate interaction, as revealed by the strict dependence on the presence of the carbohydrate-binding subunit of the lectin and the reduction of the effect of the lectin in the presence of the specific lectin-binding sugar as well as anti-lectin antibodies. Increased cytokine levels in serum of patients after injection of optimal lectin doses corroborated the in vitro results. Thus, these data provide an explanation for the increases in cellular parameters of the host defense system in vivo , which presents a further step toward their potentially beneficial clinical exploitation in standardized regimens.

Peroxisomal protein import is conserved between yeast, plants, insects and mammals.

Abstract: We have previously demonstrated that firefly luciferase can be imported into peroxisomes of both insect and mammalian cells. To determine whether the process of protein transport into the peroxisome is functionally similar in more widely divergent eukaryotes, the cDNA encoding firefly luciferase was expressed in both yeast and plant cells. Luciferase was translocated into peroxisomes in each type of organism. Experiments were also performed to determine whether a yeast peroxisomal protein could be transported to peroxisomes in mammalian cells. We observed that a C-terminal segment of the yeast (Candida boidinii) peroxisomal protein PMP20 could act as a peroxisomal targeting signal in mammalian cells. These results suggest that at least one mechanism of protein translocation into peroxisomes has been conserved throughout eukaryotic evolution.

Neutrophil chemotactic factor (IL-8) gene expression by cytokine-treated retinal pigment epithelial cells.

Abstract: The neural-derived retinal pigment epithelium (RPE) underlies the sensory retina and is central to both retinal homeostasis and many common retinal diseases. Retinal pigment epithelium cells are actively phagocytic and share several features with macrophages that have recently been shown to produce a neutrophil chemotactic factor (NCF), also known as interleukin-8, after cytokine stimulation. Because RPE cell responses to cytokines are largely unknown, human RPE cell NCF production was monitored after interleukin-1-beta (IL-1 beta), tumor necrosis factor-alpha, or lipopolysaccharide stimulation. RPE NCF mRNA expression and RPE production of biologically active NCF was time and concentration dependent. Maximal NCF mRNA expression occurred at 20 ng/ml for IL-1 beta. Messenger RNA expression in RPE cells and biologically active NCF in RPE cell supernatants were found 1 hour after stimulation and were maintained for 24 hours. These findings demonstrate that cytokine-stimulated RPE cells may evoke or augment neutrophil-mediated inflammation by synthesizing NCF, a cytokine that may be important in ocular disease mechanisms.

Reactive silicone and/or fluorine containing hydrophilic prepolymers and polymers thereof

Abstract: Vinyl unsaturated copolymers are described which are obtained in a two-step process and which consist of monomeric units A, B, C, D and E, copolymerized in a first step, and in a second step reacted with a reactive vinyl monomer M v , and in which A is a siloxane or fluorine containing vinyl monomer, 30-70% by weight; B is N,N-dimethylacrylamide or N-vinylpyrrolidone, 30-70% by weight; C is an active hydrogen containing vinyl monomer, 0.5-25% by weight; D are other copolymerizable comonomers, 0-30% by weight, and E is a chain transfer agent, 0-10 mol percent. M v is a vinyl unsaturated isocyanate. These vinyl unsaturated polymers are useful, either by themselves or in combination with other copolymerizable vinyl monomers, as heat or UV-curable coatings or glass, plastic, wood, paper, textiles, metal or ceramics, said coatings possessing low surface energies and low refractive indices. They are especially useful as UV-curable hydrophilic coatings and water-swelling biocompatible polymers, especially fully molded highly oxygen-permeable contact lenses.

Pharmacokinetics of recombinant interleukin 2 in humans.

Abstract: This report summarizes the pharmacokinetics in humans of recombinant interleukin 2 (IL-2) given as an iv bolus, iv or ip infusion, and im or sc injection Immediately after an iv bolus the serum IL-2 level equals the dose divided by the plasma volume, in a typical human 650 units/ml for a dose of 10(6) units/m2 The level initially decreases with a half-life of 129 min, followed by a slower phase with a half-life of 85 min out to 4 h after the bolus The median steady state level during an iv infusion of 10(6) units/m2 over 6 h is 41 units/ml A clearance rate of approximately 120 ml/min is obtained from either the iv bolus or infusion data and is consistent with the renal filtration being the major route of clearance Serum levels remain fairly constant for about 8 h after sc or im injection but are approximately 2% of the level seen immediately after an iv bolus The area under the time-concentration curve suggests that about 30% of the IL-2 activity is transported from the site of an im injection to the blood After ip infusion IL-2 is only slowly transported to the blood The median serum IL-2 levels are 430-fold lower than levels in the ip fluid and decrease with a median half-life of 63 h

Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein.

Abstract: Activating mutations in the gene for the alpha-chain of Gs, the stimulatory regulator of adenylyl cyclase, have been identified in human GH-secreting pituitary tumors. Using the polymerase chain reaction and allele-specific oligonucleotide hybridization, we screened 25 GH-secreting tumors for the presence of the activating mutations. We also reviewed the clinical charts of the patients from whom the tumors were removed. Of 25 tumors, 10 (40%) contained activating mutations. Patients in the mutation-positive group came to surgery with smaller tumors and had lower GH levels. The activating mutations identify a subgroup of GH-secreting pituitary tumors that probably arise from a shared oncogenic mechanism.

An improved method for determining proteoglycans synthesized by chondrocytes in culture.

Abstract: An improved micro method for measuring sulfated glycosaminoglycans (S-GAG) in chondrocyte cultures using 1,9-Dimethylmethylene Blue (DMB) has been developed. By increasing the protein concentration in the DMB assay a soluble GAG-DMB complex is prolonged. Without bovine serum albumin (BSA) in the phosphate-buffered saline (PBS) medium, the half time for loss of absorbance was 18 min; with 1% BSA-PBS there was no loss of absorbance over this time period. The limit of detection in a 96 well microtiter plate assay was 2 micrograms/ml; for a cuvette assay it was 1 microgram/ml. Collagen, DNA and RNA did not interfere with this assay. Hyaluronate caused an increase in absorbance at 530 nm that was lost by preincubating with Streptomyces hyaluronidase. The increase in absorbance was due to a turbidity change because there was no color shift from 600 to 530 nm but rather a uniform increase in absorbance between 400 to 700 nm. To validate the assay, the S-GAG was measured in conditioned medium from primary bovine articular chondrocyte monolayer cultures. A protein synthesis inhibitor, cycloheximide, blocked proteoglycan synthesis by greater than 90%. A cytokine, Interleukin-1 alpha, caused a dose-dependent decrease in proteoglycan accumulation. Chondroitinase ABC digestion of the chondrocyte conditioned medium completely prevented reactivity with the DMB. By preincubating samples with specific enzymes, different types of S-GAG can be measured with this assay. This assay can be used to measure changes in proteoglycans synthesized by chondrocytes.

CGP 37849 and CGP 39551: novel and potent competitive N-methyl-D-aspartate receptor antagonists with oral activity

Abstract: 1 The pharmacological properties of CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid; 4-methyl-APPA) and its carboxyethylester, CGP 39551, novel unsaturated analogues of the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoate (AP5), were evaluated in rodent brain in vitro and in vivo. 2 Radioligand binding experiments demonstrated that CGP 37849 potently (Ki 220nM) and competitively inhibited NMDA-sensitive L-[3H]-glutamate binding to postsynaptic density (PSD) fractins from rat brain. It inhibited the binding of the selective NMDA receptor antagonist, [3H]-(±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), with a Ki of 35nM, and was 4, 5 and 7 fold more potent than the antagonists ((±)-cis-4-phosphonomethylpiperidine-2-carboxylic acid) (CGS 19755), CPP and D-AP5, respectively. Inhibitory activity was associated exclusively with the trans configuration of the APPA molecule and with the D-stereoisomer. CGP 39551 showed weaker activity at NMDA receptor recognition sites and both compounds were weak or inactive at 18 other receptor binding sites. 3 CGP 37849 and CGP 39551 were inactive as inhibitors of L-[3H]-glutamate uptake into rat brain synaptosomes and had no effect on the release of endogenous glutamate from rat hippocampal slices evoked by electrical field stimulation. 4 In the hippocampal slice in vitro, CGP 37849 selectively and reversibly antagonized NMDA-evoked increases in CA1 pyramidal cell firing rate. In slices bathed in medium containing low Mg2+ levels, concentrations of CGP 37849 upto 10 μM suppressed burst firing evoked in CA1 neurones by stimulation of Schaffer collateral-commissural fibres without affecting the magnitude of the initial population spike; CGP 39551 exerted the same effect but was weaker. In vivo, oral administration to rats of either CGP 37849 or CGP 39551 selectively blocked firing in hippocampal neurones induced by ionophoretically-applied NMDA, without affecting the responses to quisqualate or kainate. 5 CGP 37849 and CGP 39551 suppressed maximal electroshock-induced seizures in mice with ED50S of 21 and 4 mgkg-1 p.o., respectively. 6 CGP 37849 and CGP 39551 are potent and competitive NMDA receptor antagonists which show significant central effects following oral administration to animals. As such, they may find value as tools to elucidate the roles of NMDA receptors in brain function, and potentially as therapeutic agents for the treatment of neurological disorders such as epilepsy and ischaemic brain damage in man.

Synthesis and quantitative structure-activity relationships of diclofenac analogues.

Abstract: The synthesis of a series of 2-anilinophenylacetic acids, close analogues of diclofenac, is described. These compounds were tested in two models used for evaluating the activity of nonsteroidal antiinflammatory drugs (NSAID's), inhibition of cyclooxygenase enzyme activity in vitro, and adjuvant-induced arthritis (AdA) in rats. Statistically significant correlations were found between the inhibitory activities of the compounds in these two models, indicating that cyclooxygenase inhibition seems to be the underlying mechanism for the antiinflammatory activity of these compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the crucial parameters for activity in both models were the lipophilicity and the angle of twist between the two phenyl rings. Optimal activities were associated with halogen or alkyl substituents in both ortho positions of the anilino ring. Compounds with OH groups in addition to two ortho substituents or compounds with only one or no ortho substituents were less active.

Simultaneous production of interleukin 2, interleukin 4 and interferon-γ by activated human blood lymphocytes

Abstract: The production of interleukin 2 (IL 2), IL 4 and interferon-gamma (IFN-gamma) by in vitro activated unselected human blood mononuclear cells was studied at a single-cell level. Individual lymphokine-synthesizing cells were identified by intracellular immunofluorescent staining using cytokine-specific monoclonal or polyclonal antibodies. Cultures from adult blood donors revealed a biphasic kinetic production pattern for IL 2 and IFN-gamma with peaks occurring 4-6 and 24-30 h after initiation of the cultures. Approximately 20%-40% of the lymphocytes produced IL 2 and IFN-gamma. In contrast, only 1%-3% of the lymphocytes synthesized IL 4 with maximal frequency after 6 h of culture. CD4+ as well as CD8+ T cells contributed to the synthesis of all three lymphokines studied. CD4+CD45R- T cells were the major producers of IL 2 and IL 4, while CD8+CD45R- T cells were the most common phenotype of IFN-gamma-synthesizing cells. By performing two-color immunofluorescence studies we observed that among IL 4-producing cells every second one made simultaneously IL 2 and every fourth one made IFN-gamma. Mononuclear cells from umbilical cord blood could be stimulated to make IL 2 to the same extent as cells from adult blood donors. No IL 4 production and a strikingly reduced frequency of IFN-gamma producers were noted in cell cultures from neonates. IL 2, IL 4 and IFN-gamma accumulated in the Golgi system, which resulted in a characteristic morphology of the staining, eliminating problems with evaluation of background signals.

Percutaneous absorption enhancement of an ionic molecule by ethanol-water systems in human skin.

Abstract: Ethanol–water systems enhance permeation of ionic solutes through human stratum corneum. Optimum enhancement of salicylate ion permeation has been observed with ethanol volume fractions near 0.63. The mechanism of action of ethanol–water systems enhancing skin permeation was investigated by in vitro skin permeation studies combined with Fourier transform infrared spectroscopy experiments. The increased skin permeation of the ionic permeant by the ethanol–water systems may be associated with alterations involving the polar pathway. Polar pathway alterations may occur in either or both the lipid polar head and proteinaceous regions of the stratum corneum. Ion-pair formation may also contribute to increased permeation. However, the decreased permeation of salicylate ion observed at higher volume fractions of ethanol may be attributed to decreased uptake of permeant into the stratum corneum.

Laser marking of ceramic materials, glazes, glass ceramics and glasses

Abstract: A method of laser marking ceramic materials, glazes, glass ceramics and glasses that contain at least one radiation-sensitive additive, utilizing a laser beam as radiation energy source which is either applied to, or focused on, the surface of the material to be marked in accordance with the form of the graphic symbols to be reproduced, such that a change in color is induced at the irradiated areas, wherein the wavelength of said laser beam used as energy source is in the near UV and/or visible range and/or infra-red range, and the radiation-sensitive additive is an inorganic pigment.

Lubricating oil composition

Abstract: Phosphite-free lubricating oil composition which comprises a) a mineral oil or a synthetic oil or a mixture thereof, and b) a mixture containing at least one aromatic amine of the formula (I), (I), in which R1, R2, R3 and R3' are as defined in claim 1, and at least one phenol of the formula (II), in which R4, R5 and A are as defined in claim 1, and the compounds are present in the mixture in a ratio of 2 to 6 parts by weight of the aromatic amine(s) of the formula I to 1 part by weight of the phenol(s) of the formula II The lubricating oil compositions are highly resistant to ageing and areeffective in preventing black sludge formation

3-phenylbenzofuran-2-ones

Abstract: Novel compounds of the formula I ##STR1## in which R 1 is C 13 -C 30 alkyl, R 2 is hydrogen, C 1 -C 10 alkyl, C 5 -C 12 cycloalkyl, C 5 -C 7 cycloalkyl which is substituted by C 1 -C 4 alkyl, or is phenyl or C 7 -C 12 phenylalkyl, R 3 is hydrogen or C 1 -C 4 alkyl and Z is phenyl, phenyl which is substituted by C 1 -C 8 alkyl, C 1 -C 4 alkoxy or chlorine, a group ##STR2## in which n is 1 or 2 or a group ##STR3## in which the radicals A independently of one another are C 1 -C 8 alkyl, methoxy or ethoxy, are suitable for stabilizing organic material against oxidative, thermal and actinic degradation.