Showing papers by "Novartis published in 1991"

A uniform decimal code for growth stages of crops and weeds

Abstract: Summary A universal scale (to be known as the BBCH scale) using a decimal code for the description of the growth stages of most agricultural crops and weeds is proposed. The scale and codes are based on the well-known Zadoks code for cereals. Developmentally similar growth stages of different crops are given the same codes. The general scale provides a framework within which more specific scales for individual crops may be constructed. The uniformity of the scale makes it easy to remember and use in agricultural practice and simplifies storage and retrieval in a computer system. A description of the general scale is given followed by specific scales for cereals, rice, maize, oilseed rape, field beans, peas and sunflower. Comparisons with scales currently in use are given where appropriate.

GABA B autoreceptors regulate the induction of LTP

Abstract: UNDERSTANDING the mechanisms involved in long-term potenti-ation (LTP) should provide insights into the cellular and molecular basis of learning and memory in vertebrates1. It has been established that in the CA1 region of the hippocampus the induction of LTP requires the transient activation of the N-methyl-D-aspartate (NMDA) receptor system2. During low-frequency transmission, significant activation of this system is prevented by γ-aminobutyric acid (GABA) mediated synaptic inhibition3,4 which hyperpolarizes neurons into a region where NMDA receptor-operated channels are substantially blocked by Mg2+ (refs. 5, 6). But during high-frequency transmission, mechanisms are evoked that provide sufficient depolarization of the postsynaptic membrane to reduce this block7 and thereby permit the induction of LTP. We now report that this critical depolarization is enabled because during high-frequency transmission GABA depresses its own release by an action on GABAB autoreceptors, which permits sufficient NMDA receptor activation for the induction of LTP. These findings demonstrate a role for GABAB receptors in synaptic plasticity.

Tissue-preferential promoters

Abstract: DNA sequences are able to function as promoters of tissue-preferential transcription of associated DNA sequences in plants, particularly in the roots. These DNA sequences can be used in transformation vectors to produce transgenic plants which will express the heterologous genes preferentially in tissue, particularly in the roots of maize plants.

Clomipramine in the treatment of patients with obsessive-compulsive disorder

Abstract: Two double-blind studies at 21 centers evaluated the therapeutic efficacy, safety, and tolerability of up to 300 mg/d of clomipramine hydrochloride or an equivalent number of placebo capsules in the treatment of 520 patients with obsessive-compulsive disorder, of whom 239 had had the disorder for at least 2 years (study 1) and 281 had been ill for at least 1 year (study 2). On the two principal measures of the severity of the disorder, ie, the Yale-Brown Obsessive Compulsive Scale and the National Institute of Mental Health Global Obsessive Compulsive Scale, clomipramine was significantly more effective than placebo in both studies. The mean reduction in the Yale-Brown Obsessive Compulsive Scale score at the end of 10 weeks of treatment was 38% and 44% in studies 1 and 2, respectively, for the clomipramine-treated patients and 3% and 5% for the placebo-treated patients. The drug was also found to be superior on the basis of the physicians' and patients' evaluations of global therapeutic change. The most frequently observed adverse effects during clomipramine therapy were those typically associated with tricyclic antidepressant drugs. Although uncommon, the occurrence of seizures and elevated aminotransferase values are potentially serious side effects of clomipramine. Clomipramine was generally well tolerated and was effective in reducing obsessive and compulsive symptoms.

Differential expression of TGF beta 1, beta 2 and beta 3 genes during mouse embryogenesis.

Abstract: We have examined by Northern analysis and in situ hybridisation the expression of TGF beta 1, beta 2 and beta 3 during mouse embryogenesis. TGF beta 1 is expressed predominantly in the mesodermal components of the embryo e.g. the hematopoietic cells of both fetal liver and the hemopoietic islands of the yolk sac, the mesenchymal tissues of several internal organs and in ossifying bone tissues. The strongest TGF beta 2 signals were found in early facial mesenchyme and in some endodermal and ectodermal epithelial cell layers e.g., lung and cochlea epithelia. TGF beta 3 was strongest in prevertebral tissue, in some mesothelia and in lung epithelia. All three isoforms were expressed in bone tissues but showed distinct patterns of expression both spatially and temporally. In the root sheath of the whisker follicle, TGF beta 1, beta 2 and beta 3 were expressed simultaneously. We discuss the implication of these results in regard to known regulatory elements of the TGF beta genes and their receptors.

The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.

Abstract: Cyclosporin A bound to the presumed receptor protein cyclophilin was studied in aqueous solution at pH 6.0 by nuclear magnetic resonance spectroscopy using uniform {sup 15}N- or {sup 13}C-labeling of cyclosporin A and heteronuclear spectral editing techniques. With an input of 108 intramolecular NOEs and four vicinal {sup 3}J{sub HN{alpha}} coupling constants, the three-dimensional structure of cyclosporin A bound to cyclophilin was calculated with the distance geometry program DISMAN, and the structures resulting from 181 converged calculations were energy refined with the program FANTOM. A group of 120 conformers was selected on the basis of the residual constraint violations and energy criteria to represent the solution structure. The average of the pairwise root-mean-square distances calculated for the backbone atoms of the 120 structures was 0.58 {angstrom}. The structure represents a novel conformation of cyclosporin A, for which the backbone conformation is significantly different from the previously reported structures in single crystals and in chloroform solution. The structure has all peptide bonds in the trans form, contains no elements of regular secondary structure and no intramolecular hydrogen bonds, and exposes nearly all polar groups to its environment. The root-mean-square distance between the backbone atoms of the crystal structure of cyclosporin Amore » and the mean of the 120 conformers representing the NMR structure of cyclosporin A bound to cyclophilin is 2.5 {angstrom}.« less

Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120.

Abstract: The spectrum of human immunodeficiency virus type 1 (HIV-1) isolates neutralized by antibodies from HIV-1-infected humans is broader than the spectrum of isolates neutralized by sera from animals immunized with purified gp120 subunits. This broader neutralization was due, in part, to the presence of antibodies to conserved gp120 conformational epitopes. Purified conformation-dependent gp120-specific human antibodies neutralized a wider range of virus isolates than human antibodies directed to linear determinants in gp120 and were also responsible for the majority of the gp120-specific CD4-blocking activity of HIV-1-infected human sera. A gp120 subunit vaccine that effectively presents these conformation-dependent neutralization epitopes should protect against a broader range of HIV-1 variants than a vaccine that presents exclusively linear determinants.

Angiotensin-converting enzyme inhibitor versus angiotensin II, AT1 receptor antagonist. Effects on smooth muscle cell migration and proliferation after balloon catheter injury.

Abstract: The angiotensin-converting enzyme (ACE) inhibitor, benazeprilat and the angiotensin II (Ang II), AT1-specific receptor antagonist, DuP753, were compared for their effects on intimal lesion formation as well as smooth muscle cell (SMC) proliferation and migration in Sprague Dawley rats after carotid balloon injury. Both the ACE inhibitor (benazeprilat, 3 mg/kg/day) and the AT1 antagonist (DuP 753, 10 mg/kg/day) significantly reduced intimal lesion formation after balloon injury (by 35% and 49%, respectively). Medial SMC proliferation after injury was reduced 53% by the AT1 antagonist; however, the ACE inhibitor had no effect on SMC proliferation. SMC migration was reduced 94% by the AT1 antagonist and 68% by the ACE inhibitor. These data demonstrate the importance of Ang II in SMC proliferation and migration after balloon injury. They also demonstrate that in the balloon injury model, the ACE inhibitor reduced intimal lesion size by inhibiting SMC migration alone without affecting SMC proliferation. A more pronounced reduction in lesion size was obtained after AT1 antagonism, however, when both SMC migration and proliferation were inhibited.

High-level expression of a tobacco chitinase gene in Nicotiana sylvestris. Susceptibility of transgenic plants to Cercospora nicotianae infection.

Abstract: Endochitinases (E.C. 3.2.14, chitinase) are believed to be important in the biochemical defense of plants against chitin-containing fungal pathogens. We introduced a gene for class I (basic) tobacco chitinase regulated by Cauliflower Mosaic Virus 35S-RNA expression signals into Nicotiana sylvestris. The gene was expressed to give mature, enzymatically active chitinase targeted to the intracellular compartment of leaves. Most transformants accumulated extremely high levels of chitinase-up to 120-fold that of non-transformed plants in comparable tissues. Unexpectedly, some transformants exhibited chitinase levels lower than in non-transformed plants suggesting that the transgene inhibited expression of the homologous host gene. Progeny tests indicate this effect is not permanent. High levels of chitinase in transformants did not substantially increase resistance to the chitin-containing fungus Cercospora nicotiana, which causes Frog Eye disease. Therefore class I chitinase does not appear to be the limiting factor in the defense reaction to this pathogen.

Enantioselective synthesis using chiral heterogeneous catalysts.

Abstract: The application of solid chiral catalysts for the enantioselective synthesis of chiral molecules is reviewed. An attempt has been made to discuss critically the scope and limitations of these catalytic systems and their value for the synthetic organic chemist. The different catalytic systems described in the literature are tabulated and the enantioselectivities observed for different reactions are summarized according to the functional group which is transformed. Conclusions concerning synthetic and commercial-scale applications and some ideas on the mode of action of chiral solid catalysts are presented.

Expression, structure, and function of the CD23 antigen.

Abstract: Publisher Summary The chapter explains that the structure of CD23 predicts both a lectin activity and a role in cellular adhesion. However, this view requires more experimental support, and, moreover, the binding to IgE does not require carbohydrate interactions. Interestingly, all the well-documented functions of CD23 (antigen presentation, parasite killing, and mediator release) are IgE dependent whereas most of the functions ascribed to sCD23 are clearly IgE independent. A hallmark of the CD23 molecule is that this transmembrane glycoprotein is continuously cleaved into soluble fragments, referred to as soluble CD23 (sCD23) that are released in the extracellular fluid. Most intriguingly, the two forms of CD23 may have different and sometimes antagonistic functions. In humans, some sCD23 fragments retain the ability to bind to IgE and have therefore been named IgE-binding factors (IgE–BFs). Human CD23 is a single-chain 45-kDa glycoprotein; it contains one chain of N-linked carbohydrates of the complex type, several O-linked carbohydrates, and sialic acid residues. Immunoprecipitation studies using either anti-CD23 Mab orIgE reveal the presence of three components with masses of 60–95, 45, and 37 kDa. The high-molecular-weight component is because of the formation of aggregates of the 45-kDa molecules after solubilization of the cells. Indeed, the molecules of 45 and 60–95 kDa display identical peptide maps and they share several antigenic determinants. This chapter discusses the functions of membrane CD23 and soluble CD23. In healthy individuals the serum level of sCD23 remains stable over a long period of time, indicating that it is not affected by environmental factors. CD23 is found at low levels on the majority of mature resting B cells, and freshly isolated PBMCs express only type a CD23 mRNA.

Induced Systemic Resistance in Cucumber in Response to 2,6-Dichloro-Isonicotinic Acid and Pathogens

Abstract: 2,6-dichloro-isonicotinic acid (CGA 41396) and its ester derivative (CGA 41397) induce local and systemic resistance in cucumber against C. lagenarium as well as other pathogens. These compounds have no direct fungicidal effet comparable to standard fungicides and extracts from treated plants do not show the presence of fungitoxic metabolites. In addition both compounds modify the physiology of the host plant by inducing chitinase. Thus CGA 41396 and 41397 could be considered as novel inducers of resistance.

Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease.

Abstract: A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-alpha]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-alpha]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5 nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

Long-Term Human Immunodeficiency Virus Infection in Asymptomatic Homosexual and Bisexual Men with Normal CD4+ Lymphocyte Counts: Immunologic and Virologic Characteristics

Abstract: From a prospective cohort study, 24 asymptomatic men were identified who had been antibody positive for human immunodeficiency virus (HIV) for at least 5 years (median = 9.1) with CD4+ lymphocyte counts greater than or equal to 400 cells/mm3. Of these "nonprogressors", 23 (96%) had evidence of HIV infection by either HIV culture or the polymerase chain reaction (PCR) for HIV DNA, although only 1 (4%) had a positive assay for HIV RNA (by PCR) and no one was positive for p24 antigen. Compared with 24 antibody-negative men and 14 men with AIDS, nonprogressors had higher CD8+ counts and lower natural killer cell activity. Nonprogressors had higher beta 2-microglobulin levels than did seronegative controls, suggesting some degree of immune system activation. Compared with men with AIDS, nonprogressors seemed to have a stronger antibody response to six different HIV-related proteins but did not differ significantly in neutralizing antibody or antibody-dependent cellular cytotoxic activity.

Isoprenoid modification of rab proteins terminating in CC or CXC motifs.

Abstract: Mevalonate starvation of hamster fibroblasts resulted in a shift of rab1b from the membrane to the cytosolic fraction, suggesting that rab1b depends upon an isoprenoid modification for its membrane localization. rab1b and rab3a proteins expressed in insect cells incorporated a product of [3H]mevalonate, and gas chromatography analysis of material released by Raney nickel cleavage demonstrated that rab1b and rab3a are modified by geranylgeranyl groups. Additionally, in vitro prenylation analysis demonstrated farnesyl modification of H-ras but geranylgeranyl modification of five rab proteins (1a, 1b, 2, 3a, and 6). Together, these results suggest that the carboxyl-terminal CC/CXC motifs (X = any amino acid) specifically signal for addition of geranylgeranyl, but not farnesyl, groups. A rab1b mutant protein lacking the two carboxyl-terminal cysteine residues was not prenylated in vitro. However, since a mutant H-ras protein that terminates with tandem cysteine residues was also not modified, the CC motif may be essential, but not sufficient, to signal prenylation of rab1b. Finally, rab1b and rab3a proteins were not efficient substrates for either farnesyl- or geranylgeranyltransferase activities that modify CAAX-containing proteins (A = any aliphatic amino acid). Therefore, rab proteins may be modified by a prenyltransferase(s) distinct from the prenyltransferases that modify carboxyl-terminal CAAX proteins.

Staurosporine derivatives substituted at methylamino nitrogen

Abstract: N-substituted derivatives of staurosporine of the general formula [Stau]--N(CH.sub.3)--R (I) in which [Stau] represents a residue of the partial formula ##STR1## and R represents a hydrocarbyl radical R o or an acyl radical Ac, which radicals preferably have a maximum of 30 carbon atoms, and salts of compounds of the formula I having salt-forming properties, are distinguished as selective inhibitors of proteinkinase C. They are manufactured by conventional alkylation or acylation, respectively, of staurosporine.

Enantioselective Hydrogenation of Ethyl Pyruvate: Effect of Catalyst and Modifier Structure

Abstract: The effect of catalyst and modifier structure on selectivity and activity for the enantioselective hydrogenation of ethyl pyruvate with cinchona modified Pt/Al2O3 catalysts has been investigated. It has been found that the platinum dispersion and the method of catalyst preparation have a decisive influence on the catalytic performance. In order to get high optical yields, the platinum dispersion should be lower than 0.2 - 0.3. The texture of the support is less important but must be optimized with respect to pore size in order to get high enantioselectivity. Modifiers derived from cinchonidine lead to an excess of (R)-ethyl lactate while cinchonine gives preferentially the S enantiomer. Changes in the O-C9-C8-N part of the cinchona alkaloid have a decisive influence both on sign and size of the optical induction while the nature of the substituent in the quinuclidine part, R1, has only a minor effect. Partial hydrogenation of the quinoline rings results in a decreased enantioselectivity. Conclusions concerning the mode of action of the enantioselective catalyst are discussed.

Elevated plasma levels of hyaluronate in patients with osteoarthritis and rheumatoid arthritis.

Abstract: Plasma levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA), measured by enzyme-linked immunosorbent assay, were compared with levels in a healthy, age-matched non-arthritic control group, in a retrospective study. Compared with the controls, the mean level of plasma HA was sevenfold higher in the RA group and twofold higher in the OA group. There was no statistically significant correlation between HA levels and 7 other clinical and biochemical parameters in patients with RA. In the OA group, however, plasma HA levels were found to correlate with an objective functional capacity score and with an articular index based on the total amount of cartilage in involved joints. In a retrospective longitudinal study of 6 patients with RA, plasma levels of HA did not show a significant correlation with plasma levels of elastase or with the erythrocyte sedimentation rate. These data support in part the contention that plasma HA may be unique as a marker, in that it may be a reflection of synovial involvement and inflammation, rather than only of inflammation, in arthritis.

Apparatus for processing or preparing liquid samples for chemical analysis

Abstract: An apparatus (1) for processing or preparing liquid samples for a preferably quantitative chemical analysis, especially for flow-injection analysis, is, for the purpose of miniaturisation and reducing the necessary sample volume while at the same time reducing the analysis time, assembled from a set of plate-like components (8). Each of the components (8) includes channels to form pipe pieces (9) and/or branches (13) with orifices and/or values, for example non-return valves, and/or pumps (6,7) in order to be able to feed the carrier liquid and sample to a detector (3) in the desired manner. Depending on the purpose of the analysis, the components (8) with the pipes and functional parts contained in them may be stacked in varying number and/or sequence and/or angular orientation relative to one another and can be connected in a sealing manner in the operative position.

Instrumented Impact and Static Indentation of Composites

Abstract: The low velocity impact behavior of several laminate systems has been studied. Instrumented impact tests were compared with static indentation tests using the same specimen and test configurations. The impact behavior, defined by impact force, damage size and energy absorption, was found to be similar to the static indentation response. The damage growth process during impact as the force surged to its maximum value can be visualized from the static indentation damage induced at incrementally increased force levels. Delamination impact damage suddenly appeared only when the impact force reached a threshold value which was dependent on laminate fracture toughness. Further force increase resulted in gradual damage size growth until fiber damage caused the force to level off. There was evidence that laminate fracture toughness also affected the level-off force. Fiber damage not only absorbed significant energy but also allowed for further delamination damage growth. Overall, the characteristics of impact for...