Showing papers by "Novartis published in 1994"

Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers

Abstract: CYTOGENETIC abnormalities of chromosome 9p21 are characteristic of malignant melanomas1,2, gliomas3, lung cancers4 and leukaemias5. From a panel of 46 human malignant cell lines, we localized by positional cloning the most frequently deleted region on 9p21. Sequence analysis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cyclin-dependent kinase 4 (CDK4) 6. Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. One carcinoma had a deletion entirely within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line nonsense mutation. The CDK4 inhibitor is thought to be a physiological suppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.

A Central Role of Salicylic Acid in Plant Disease Resistance

Abstract: Transgenic tobacco and Arabidopsis thaliana expressing the bacterial enzyme salicylate hydroxylase cannot accumulate salicylic acid (SA). This defect not only makes the plants unable to induce systemic acquired resistance, but also leads to increased susceptibility to viral, fungal, and bacterial pathogens. The enhanced susceptibility extends even to host-pathogen combinations that would normally result in genetic resistance. Therefore, SA accumulation is essential for expression of multiple modes of plant disease resistance.

Dinucleoside phosphinates and their pharmaceutical compositions

Abstract: A dinucleotide analogue of formula ##STR1## where B1 and B2 are each independently a monovalent nucleoside base radical; R1 is R1 a or Z; R1 a, R2, R3 and R4 are each independently hydrogen, halogen or hydroxy; R5 is R5 a or Z; R6 is hydrogen or R6 a ; R7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R7 a, R8 is R8 a or Z, or the indicated R7 O and R8 together denote an isopropylidenedioxy group; R5 a and R8 a are each independently hydrogen, halogen, hydroxy, --OR10, --OCOR10 or silyloxy substituted by three C1 -C15 hydrocarbyl groups; R6 a and R7 a are each independently a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C30 araliphatic radical, --COR11, --SO2 R11 or silyl substituted by three C1 -C15 hydrocarbyl groups; R9 is hydrogen, a C1 -C8 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion; R10 and R11 are each independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical; Rx and Ry are independently hydrogen, halogen, hydroxy, a C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl, C7 -C16 aralkyl, C1 -C10 alkoxy, C2 -C10 alkenoxy, C6 -C10 aryloxy or C7 -C16 aralkyloxy group, which is substituted or unsubstituted, or --OCORz ; Rz is a substituted or unsubstituted C1 -C10 alkyl, C2 -C10 alkenyl, C3 -C8 cycloalkyl, C6 -C15 aryl or C7 -C16 aralkyl group; and Z is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being substituted or unsubstituted.

Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer.

Abstract: The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals Similar antibody responses have been found in some normal individuals The patient with the greatest antibody response was studied in detail In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides Similar T-cell responses have been detected in additional patients It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate If immunity could be generated, the result might be destructive autoimmunity The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression

Pyrimidine derivatives and processes for the preparation thereof

Abstract: There are described N-phenyl-2-pyrimidine-amine derivatives of formula I ##STR1## wherein R 1 is 4-pyrazinyl, 1-methyl-1H-pyrrolyl, amino- or amino-lower alkyl-substituted phenyl wherein the amino group in each case is free, alkylated or acylated, 1H-indolyl or 1H-imidazolyl bonded at a five-membered ring carbon atom, or unsubstituted or lower alkyl-substituted pyridyl bonded at a ring carbon atom and unsubstituted or substituted at the nitrogen atom by oxygen, R 2 , R 3 , R 9 , X, Y, n and R 10 are defined in claim 1 These compounds can be used, for example, in the therapy of tumoral diseases

Activation of Raf-1 by 14-3-3 proteins.

Abstract: THE protein Raf-1, a key mediator of mitogenesis and differentia-tion, associates with p21*"a5 (refs 1-3). However, the regulation of the serine/threonine kinase activity of Raf-1 is still not understood4 13. Using the yeast two-hybrid system8'14"16, we identi-fied two structurally related proteins that interact with the amino-terminal region of Raf-1. These proteins, 14-3-3 £ (PLA2) and 14-3-3 p (HS1), are members of the 14-3-3 family of proteins17'23. Expression of 14-3-3 proteins in Xenopm oocytes enhanced Raf-1 activity and promoted Raf-1-dependent oocyte maturation. A dominant negative mutant of Raf-1 blocked the effects of 14-3-3 protein.

Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption.

Abstract: With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.

Why are long-acting beta-adrenoceptor agonists long-acting?

Abstract: The extended duration of bronchodilation due to formoterol and salmeterol greatly exceeds that of short acting beta 2-adrenoceptor agonists, such as salbutamol or terbutaline. This extended duration and their capacity to "reassert" airway smooth muscle relaxation in vitro despite repeated washing has prompted considerable debate on the underlying mechanism(s). The comparative pharmacology, and molecular modelling of these drugs and of the beta 2-adrenoceptor and its ligand binding core have cast doubt on the exosite/exoceptor model previously proposed to explain the behaviour of salmeterol. We present evidence supporting a unifying hypothesis that the duration of action both of formoterol and salmeterol is determined principally by their physicochemical interactions with membrane lipid bilayers (plasmalemma diffusion microkinetic model), rather than putative distinct exosite/exoceptor binding sites in or near the beta 2-adrenoceptor. This model provides a clearer understanding of the pharmacological profile of these drugs (rate of onset, duration, "reassertion", interaction with hydrophilic and hydrophobic beta 2-adrenoceptor antagonists), and explains why in human airway smooth muscle in vitro a true relaxation-concentration response may not exist for salmeterol.

Chronic effects of atrazine on estrus and mammary tumor formation in female Sprague‐Dawley and Fischer 344 rats

Abstract: The chronic effects of dietary administration of atrazine at levels as high as 400 ppm on selected endocrine and tumor profiles were evaluated in Fischer 344 and Sprague-Dawley female rats. The study showed that lifetime dietary administration of atrazine at a maximum tolerated dose (MTD) to Sprague-Dawley female rats caused (1) lengthening of the estrous cycle, (2) increased number of days in estrus or under the influence of exposure to estrogen, (3) earlier onset of galactocele formation, and (4) earlier onset of mammary and pituitary tumor formation but not an increased incidence of mammary and pituitary tumors when compared to concurrent control rats. Fischer 344 female rats fed atrazine at an MTD exhibited slightly lengthened estrous cycles, but no effects were observed on estradiol or progesterone levels, or on the onset or incidence of mammary tumors. These results support a hypothesis that high-dose atrazine administration in Sprague-Dawley females is related to an acceleration of age-related endocrine changes leading to an earlier onset and/or increased incidence of mammary tumors. This endocrine-mediated response, which appears to be unique to the Sprague-Dawley female rat, occurs only at or above a threshold dose (the MTD) that interferes with normal estrous cycling, promoting prolonged exposure to endogenous estrogen.

Parenterally administrable liposome formulation comprising synthetic lipids

Abstract: The invention relates to pharmaceutical compositions in the form of parenterally, especially intravenously, administrable liposome dispersions or dry preparations, especially lyophilisates, that can be used therefor, comprising the zinc-phthalocyanine complex and synthetic, substantially pure phospholipids.

Mineralization of the herbicide atrazine as a carbon source by a Pseudomonas strain.

Abstract: Strain YAYA6 was isolated from a mixed microbial community that was growing on atrazine as a sole carbon source and formed quantitative amounts of chloride and nitrate. This strain was identified as a member of the true pseudomonad group (RNA group I) and was given the designation DMS 93-99. The growth yield when atrazine was the sole carbon and nitrogen source was 80 g (dry weight) of cells per mol of atrazine, and the cell doubling time was around 11 h. Approximately 20% of [U-ring 14C]atrazine was mineralized during primary degradation of atrazine. After atrazine disappeared from the culture supernatant, mineralization continued until the level of mineralization was more than 50%. Under different experimental conditions 10% of the atrazine supplied initially was converted to cyanuric acid and < 1% was converted to other s-triazines after prolonged incubation. Degradation proceeded via dechlorination and N-dealkylation. Atrazine was degraded until the concentration was circa 0.1 milligrams/liter. We obtained evidence showing that strain YAYA6 has specific uptake mechanisms for atrazine but less specific degradation mechanisms for s-triazines.

7 beta-hydroperoxycholest-5-en-3 beta-ol, a component of human atherosclerotic lesions, is the primary cytotoxin of oxidized human low density lipoprotein.

Abstract: Modification of low density lipoprotein (LDL) by free radical oxidation renders this molecular complex cytotoxic. Oxidized lipoproteins exist in vivo in atherosclerotic lesions and in the plasma of diabetic animals, suggesting that lipoprotein-induced tissue damage may occur in certain diseases. We undertook purification and identification of the major cytotoxin in oxidized LDL. The lipid extract from oxidized LDL was subjected to multiple HPLC separations, and the fractions were assayed for cytotoxicity. Mass spectrometry and nuclear magnetic resonance identified the purified toxin as 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 beta-OOH-Chol). This molecule accounted for approximately 90% of the cytotoxicity of the lipids of oxidized LDL. We also found 7 beta-OOH-Chol in human atherosclerotic lesions from endarterectomy specimens obtained immediately after excision. These results are consistent with the hypothesis that the oxidized LDL present in lesions has the capacity to induce cell and tissue injury, leading to progression of the disease and the generation of the necrotic core of the lesion.

Controlled release drug delivery device

Abstract: An oral drug delivery device for delivering a drug either intermittently or to a pre-selected region of the gastro-intestinal tract, particularly to the colon, consists of an a solid core comprising an active agent coated with a delay jacket, then coated with a semi-permeable membrane which is optionally drilled to provide a release orifice, and then optionally further coated with an enteric material. The device delivers substantially all of the active agent to the targeted site.

Recombinant alphavirus vectors

Abstract: The present invention provides composition and methods for utilizing recombinant alphavirus vectors.

Mannose or xylose based positive selection

Abstract: The present invention provides a method for identifying or selecting from a population of eukaryotic cells cultivated on or in a medium containing at least one compound, cells which have a metabolic advantage as a result of having being transformed, wherein: (i) the cells are transformed with a nucleotide sequence or a co-introduced nucleotide sequence one of which comprises a region which: (a) encodes a protein which is involved in the metabolism of the compound, and/or (b) regulates the activity of the protein; and (ii) the compound is mannose or xylose or a derivative or a precursor of these, or a substrate of the protein, or is capable of being metabolized by the transformed cells into such a substrate, with the proviso that the compound is not mannos when the proteine is mannose 6 phosphate isomerase. The invention also includes a method according to the preceding paragraph wherein the compounds are are not so limited with the proviso that an agent which reduces the toxicity to the cells of the compound is added to the medium. It is preferred that where a toxicity-reducing agent has been added to the culture medium, the compound is mannose and the nucleotide or co-introduced nucleotide sequence encodes mannose-6-phosphate isomerase.

Nucleoside phosphinate compounds and compositions

Abstract: A compound of formula ##STR1## where R1 is hydrogen or a protecting group Q; R2 is hydrogen, a C1 -C8 aliphatic radical, a C6 -C15 aromatic radical, a C3 -C8 cycloaliphatic radical, a C7 -C13 araliphatic radical, an alkali metal ion or an ammonium ion; R3 and R4 are independently hydrogen, halogen or hydroxy; R5 is C6 -C10 aryloxythiocarbonyloxy, the C6 -C10 aryl group being unsubstituted or substituted, or R5 a ; R5 a is hydrogen, fluorine, chlorine, hydroxy, --OR8, --OCOR8 or silyloxy substituted by three C1 -C15 hydrocarbyl groups; R6 is hydrogen, a C1 -C10 aliphatic radical, a C6 -C15 aromatic radical, a C7 -C16 araliphatic radical, --COR9, --SO2 R9 or silyl substituted by three C1 -C15 hydrocarbyl groups; R7 is a monovalent nucleoside base radical, hydroxyl, --OR8 or --OCOR8, and R9 are independently a C1 -C10 aliphatic radical, a C3 -C8 cycloaliphatic radical, a C6 -C15 aromatic radical or a C7 -C16 araliphatic radical; or R5 and the indicated R6 O-together denote an isopropylidenedioxy group or R5 and R7 together denote an isopropylidenedioxy group, provided that when R5 and R7 together denote isopropylidenedioxy, R1 R2, R3 R4 and R6 are not all hydrogen. The disclosure further relates to a method of preparing the compounds of formula I by reacting a olefinic acetonide with a phosphinate compound and to the use of the compounds of formula I as pharmaceutical agents.

Cloning of Genes Involved in the Synthesis of Pyrrolnitrin from Pseudomonas fluorescens and Role of Pyrrolnitrin Synthesis in Biological Control of Plant Disease

Abstract: A soil isolate of Pseudomonas fluorescens (BL915) was shown to be an effective antagonist of Rhizoctonia solani-induced damping-off of cotton. Investigation of the biological basis of this antagonism revealed that the strain produces pyrrolnitrin, a secondary metabolite known to inhibit R. solani and other fungi. Mutants of strain BL915 that did not produce pyrrolnitrin and did not suppress damping-off of cotton by R. solani were generated by exposure to N-methyl-N' -nitro-N-nitrosoguanidine. A gene region that was capable of restoring pyrrolnitrin production to the non-pyrrolnitrin-producing mutants and of conferring this ability upon two other P. fluorescens strains not otherwise known to produce this compound or to be capable of suppressing damping-off caused by R. solani was isolated from strain BL915. The non-pyrrolnitrin-producing strains (mutants of BL915 and the other two P. fluorescens strains) which synthesized pyrrolnitrin after the introduction of the gene region from strain BL915 were also shown to be equal to strain BL915 in their ability to suppress R. solani-induced damping-off of cotton. These results indicate that we have isolated from P. fluorescens BL915 a gene(s) that has a role in the synthesis of pyrrolnitrin and that the production of this compound has a role in the ability of this strain to control damping-off of cotton by R. solani.

N-phosphonomethyl dipeptides and their phosphonate prodrugs, a new generation of neutral endopeptidase (NEP, EC 3.4.24.11) inhibitors

Abstract: Inhibitors of the zinc protease neutral endopeptidase (NEP, EC 3.4.24.11) offer significant therapeutic interest as antihypertensives due to their ability to potentiate the biological action of the circulating natriuretic hormone ANF (atrial natriuretic factor). N-Phosphonomethyl dipeptides bearing a central (4-phenyl)phenylalanine residue have been designed to exert potent and selective NEP inhibition. In particular, (S)-3-[N-[2- [(phosphonomethyl)amino]-3-(4-biphenylyl)propionyl]amino]propionic acid (10a) (CGS 24592) displayed high inhibitory potency in vitro (IC50 = 1.9 +/- 0.1 nM) and a long plasma half-life in rats but lacked oral bioavailability. This drawback was overcome by using esterase-sensitive (acyloxy)alkyl phosphonates. More remarkable, several diaryl phosphonate derivatives of 10a also performed as effective prodrugs. Specifically, the structurally simple diphenyl phosphonate 18 (CGS 25462) induced potent inhibition of NEP ex vivo for at least 8 h after oral administration to rats (30 mg/kg). Its antihypertensive effect was demonstrated in DOCA-salt rats. At 30 mg/kg orally, 18 caused a significant reduction in mean arterial pressure measuring -35 +/- 7 mmHg at 5-h postdosing. The alpha-aminomethyl phosphonate 18 represents a new generation of selective NEP inhibitors that combine high potency, long duration of action, and oral bioavailability. Therefore, it holds promise as a novel therapeutic agent for the treatment of human hypertension and congestive heart failure.

Clinical Uses of Insulin-like Growth Factor I

Abstract: Insulin-like growth factor I (IGF-I) has acute insulin-like metabolic effects and long-term anabolic actions. The therapeutic potential of recombinant human IGF-I treatment is being investigated in various growth hormone-resistant and insulin-resistant disorders. Recent studies have shown that IGF-I may substitute for growth hormone in promoting linear growth in children with growth hormone insensitivity. The anabolic, protein-sparing action of IGF-I is being evaluated as a potential therapy for adults with catabolic diseases. Patients with insulin-dependent diabetes mellitus have reduced endogenous IGF-I production, and studies are in progress to determine whether treatment with IGF-I in addition to insulin may improve their metabolic/anabolic status. Insulin-like growth factor I treatment may reduce glucose and triglyceride levels in adults with non-insulin-dependent diabetes mellitus and in some patients with extreme insulin resistance. Further studies are needed to evaluate the efficacy and safety of IGF-I treatment in these and other conditions and to provide a better understanding of this hormone's normal physiologic role(s) and complex relations with growth hormone and insulin.

Pyrimidineamine derivatives and processes for the preparation thereof

Abstract: N-phenyl-2-pyrimidineamine derivatives of formula (I) wherein the substituents are as defined in claim 1 are described. Those compounds can be used, for example, in the treatment of tumour diseases.

Pharmacokinetic Characterisation of Transdermal Delivery Systems

Abstract: The key aspects of the pharmacokinetics of transdermal delivery systems including time lag, steady-state plasma levels and decline phase are illustrated in this review. The 7 currently marketed transdermal systems [nitroglycerin (glyceryl trinitrate), estradiol, clonidine, fentanyl, nicotine, scopolamine (hyoscine) and estradiol/norethisterone acetate] are discussed, as are systems in development. Single-dose absolute bioavailability studies characterise the period of onset, the steady-state plateau and the declining phase, and typify transdermal delivery. More complex temporal profiles result from interactions with enhancers or removal of the system before steady-state conditions are achieved. Clinically these systems are used to achieve multiple peak serum estradiol concentrations after application of transdermal estradiol, and an initial peak systemic concentration of testosterone after application of transdermal testosterone. Multiple-dose, dose proportionality and skin site bioequivalence studies are needed for the full pharmacokinetic characterisation of a transdermal delivery system. The relationship of system design to variability is discussed. Although the data are limited, population factors, cutaneous metabolism and tolerance all appear to influence the disposition of drugs administered transdermally. For example, the route of delivery influences which nitroglycerin metabolite predominates. Futhermore, as a result of tolerance to nitrates, a transdermal delivery system must be removed for 8 to 12 hours for optimal effect. Therefore, transdermal delivery systems, designed on the basis of pharmacokinetic principles and concentration-effect relationships, have the potential to provide optimal therapy for the treatment of some conditions.

Non-toxic mucosal adjuvant

Abstract: A non-toxic mucosal adjuvant is provided which may be admixed with further antigens to provide a vaccine administrable to mucosal surfaces in organisms including man. Preferably, the non-toxic mucosal adjuvant is a detoxified mutant of a bacterial ADP-ribosylating toxin, optionally comprising one or more amino acid additions, deletions or substitutions.

Hypothesis for mammary tumorigenesis in Sprague‐Dawley rats exposed to certain triazine herbicides

Abstract: The symmetrical triazine herbicides have been used for the preemergence control of broadleaf weeds for nearly three decades. Recently, certain members of this class, primarily the chlorotriazines (substituted in the 2 position), have been shown to evoke an increased incidence of mammary tumors in female Sprague‐Dawley rats. This response was noted when these chemicals were administered in the diet for 2 yr, and most often at dietary feeding levels at or above the maximum tolerated dose (MTD). At levels exceeding the MTD the health of these animals was compromised, as manifested by toxicity‐related reduced survival that was not associated with the occurrence of mammary tumors. Mammary tumors in rats frequently occur as a result of the influence of endogenous estradiol and prolactin. Those hormones, as well as progesterone, growth‐stimulating, luteinizing, and follicle‐stimulating hormones, were measured after 24 mo of dietary administration of the chlorotriazine, simazine. The plasma hormone pattern seen i...

Process and device for the manufacture of mouldings and mouldings manufactured in accordance with that process

Abstract: A measured amount of a material that is crosslinkable by impingement of a suitable form of energy, especially UV light, is introduced into a two-part mould of which cavity determines the shape of a moulding to be produced. The two mould halves are held a small distance from one another so that a thin annular gap is formed between them, which gap is in communication with the mould cavity and through which gap excess material can escape. The crosslinking is triggered by impingement of the selected form of energy, the impingement being spatially restricted to the cavity by suitable masking so that material disposed outside the mould cavity is not crosslinked. In that manner mouldings are obtained that do not require subsequent mechanical processing, and the mould is reusable. The process is especially, but not, however, exclusively, suitable for the manufacture of contact lenses.

Constitutive expression of the virulence genes improves the efficiency of plant transformation by Agrobacterium

Abstract: Inducible virulence (vir) genes of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid are under control of a two-component regulatory system. In response to environmental factors (phenolic compounds, sugars, pH) VirA protein phosphorylates VirG, which in turn interacts with the promoters of other vir genes, causing induction. A mutation of virG, virGN54D (which codes for a Asn-54-->Asp amino acid change in the product), causes constitutive expression of other vir genes independent of virA. We have investigated whether providing Agrobacterium with a plasmid containing virGN54D augments the efficiency of transfer of the T-DNA (transferred DNA). For both tobacco and cotton, we observed an enhancement of transformation efficiency when the inciting Agrobacterium strain carries the virGN54D mutation. We also tested whether supplying Agrobacterium with a similar plasmid containing wild-type virG affects the efficiency of T-DNA transfer. An intermediate efficiency was observed when this plasmid was employed. Using a beta-glucuronidase (GUS) reporter gene to assess transient expression of T-DNA after transfer to tobacco and maize tissues, we observed a higher frequency of GUS-expressing foci after inoculation with Agrobacterium strains carrying virGN54D than with Agrobacterium carrying the wild-type virG. Gene-transfer efficiency to maize by an octopine strain was greatly improved upon introduction of virGN54D. Multiple copies of wild-type virG were equally effective in promoting transient expression efficiency in tobacco but were virtually ineffective in maize. We propose the use of virGN54D to improve the efficiency of Agrobacterium-mediated transformation, especially for recalcitrant plant species.

Insulin-Like Growth Factor-1 Lowers Protein Oxidation in Patients with Thermal Injury,

Abstract: ObjectiveThe effect of insulin-like growth factor-1 (IGF-1) on energy expenditure and protein and glucose metabolism in a group of patients with thermal injury was determined.Summary Background DataAccelerated protein catabolism is a constant feature of the hypermetabolic response to thermal injury.