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Biomedical subjects

P Meier

Publications and source records attributed to P Meier.

At least 37 records · Page 2Linked to original sources
PubMed2001

The natural transformation of the soil bacteria Pseudomonas stutzeri and Acinetobacter sp. by transgenic plant DNA strictly depends on homologous sequences in the recipient cells.

The nptII(+) gene present in the genome of transgenic potato plants transforms naturally competent cells of the soil bacteria Pseudomonas stutzeri and Acinetobacter BD413 (both harboring a plasmid with an nptII gene containing a small deletion) with the same high efficiency as nptII(+) genes on plasmid DNA (3x10(-5)-1x10(-4) transformants per nptII(+)) despite the presence of a more than 10(6)-fold excess of plant DNA. However, in the absence of homologous sequences in the recipient cells the transformation by nptII(+) dropped by at least about 10(8)-fold in P. stutzeri and 10(9)-fold in Acinetobacter resulting in the latter strain in < or =1x10(-13) transformants per nptII(+). This indicated a very low probability of non-homologous DNA fragments to be integrated by illegitimate recombination events during transformation.

Acinetobacter↗
PubMed2001

Effects of charged water-soluble polymers on the stability and activity of yeast alcohol dehydrogenase and subtilisin Carlsberg.

Remarkable increases in enzyme catalytic stability resulting from addition of charged water-soluble polymers have recently been reported, suggesting that use of these polymers may be an attractive general strategy for enzyme stabilization. To test the proposed hypothesis that coulombic forces between water-soluble polymers and enzymes are primarily responsible for enzyme stabilization, we examined the catalytic stability and activity of two enzymes in the presence of polymers differing in net charge. All polymers tested increased enzyme lifetimes, regardless of their net charge, suggesting that stabilization of these enzymes by water-soluble polymers is not solely dependent on simple electrostatic interactions between the polymers and enzymes.

Acrylic Resins↗
PubMed2001

Pars plana lentectomy for treatment of congenital cataract.

BACKGROUND: Congenital cataract surgery can be performed using a pars plicata/plana or a limbal approach, if placement of an intraocular lens at the time of cataract removal is not a consideration. Because of the high incidence of secondary cataract formation in children the operation should be combined with capsulotomy and anterior vitrectomy. METHODS: The series consisted of 30 eyes from 20 consecutive children who suffered from congenital cataract and underwent cataract surgery between May 1995 and June 2000. The inclusion criterion was congenital cataract affecting the visual axis. We performed the operations as lens aspiration with anterior and posterior capsulotomy and anterior vitrectomy via the pars plana or plicata. We used contact lenses to rehabilitate vision. All patients received intensive orthoptic and pleoptic treatment. RESULTS: This surgical technique provided in all eyes a clear visual axis. During follow-up of 3 months to 4.5 years, secondary cataract developed in five eyes. Retinal detachment, glaucoma and endophthalmitis did not occur. One patient developed contact lens intolerance and a secondary intraocular lens was placed in the ciliary sulcus. DISCUSSION: Lentectomy via a pars plana or pars plicata approach is a suitable and safe method for treating cataract in children. Our chosen method of lentectomy is an alternative to early implantation of an intraocular lens. It is possible to perform uncomplicated secondary implantation of an intraocular lens in the ciliary sulcus.

Aphakia, Postcataract↗
PubMed2001

Hidden need for drug treatment services: measuring levels of problematic drug use in the North West of England.

BACKGROUND: In the North West of England, data on drug users are routinely collected from a variety of agencies including specialist treatment centres, police and probation services. However, the covert nature of drug use means that alone, these conventional monitoring systems cannot provide the epidemiology required to target and develop drug treatment and prevention initiatives. METHODS: Utilizing surveillance data and capture-recapture techniques we estimate the rates of problematic drug users by age and sex in five North West health authorities and one local authority. RESULTS: Analyses show concentrations of problematic drug use in large metropolitan areas (Liverpool and Manchester) with levels as high as 34.5 and 36.5 per 1000 population (ages 15-44), respectively, and, for males, levels exceed 50 per 1000 in three authorities. Patterns of prevalence for those aged 25 and over differed from those in the younger age groups, with disproportionate levels of young users outside metropolitan areas. The proportion of young users already in treatment (21.3 per cent) was lower (older users, 35.3 per cent), with overall proportions in treatment varying between health authorities (range 26.2-46.5 per cent). CONCLUSION: With a multi-agency approach, established monitoring systems can be used to measure hidden populations of drug users. Estimates of the current populations of such users in the North West of England suggest that planned increases of people in treatment by 100 per cent would fail to accommodate even current level of problematic users. A holistic approach to new initiatives must ensure that the high level of relapse once drug users are discharged are reduced and that the needs of young users are addressed before prolonged treatment is required.

Adolescent↗
PubMed2000

Apoptosis in development.

Essential to the construction, maintenance and repair of tissues is the ability to induce suicide of supernumerary, misplaced or damaged cells with high specificity and efficiency. Study of three principal organisms--the nematode, fruitfly and mouse--indicate that cell suicide is implemented through the activation of an evolutionarily conserved molecular programme intrinsic to all metazoan cells. Dysfunctions in the regulation or execution of cell suicide are implicated in a wide range of developmental abnormalities and diseases.

Animals↗
PubMed2000

A finite-element model for the mechanical analysis of skeletal muscles.

In the present paper, a finite-element model for simulating muscle mechanics is described. Based on nonlinear continuum mechanics an algorithm is proposed that includes the contractile active and passive properties of skeletal muscle. Stress in the muscle is assumed to result from the superposition of a passive and an active part. The passive properties are described by a hyperelastic constitutive material law whereas the active part depends on the fibre length, shortening velocity and an activation function. The constraint of approximate incompressibility of the muscle element is satisfied as a property of the constitutive equations. Because of the nonlinear behaviour of the material and the highly dynamical performance an incremental procedure including iterative methods is used. The advantage of the model over previous formulations is the possibility to integrate the element into an engineering standard finite-element programme ANSYS using advanced numerical tools. The model allows simulations of muscle recruitment, calculations of stress and strain distributions and predictions of muscle shape. Other possible applications are studies of the muscle architecture, the effect of inertia and impacts. First, simple examples are presented.

Animals↗
PubMed2000

Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL.

Unlike other tumor necrosis factor family members, the cytotoxic ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L contains an unpaired cysteine residue (Cys(230)) in its receptor-binding domain. Here we show that the biological activity of both soluble recombinant TRAIL and cell-associated, full-length TRAIL is critically dependent on the presence of Cys(230). Mutation of Cys(230) to alanine or serine strongly affected its ability to kill target cells. Binding to its receptors was decreased by at least 200-fold, and the stability of its trimeric structure was reduced. In recombinant TRAIL, Cys(230) was found engaged either in interchain disulfide bridge formation, resulting in poorly active TRAIL, or in the chelation of one zinc atom per TRAIL trimer in the active, pro-apoptotic form of TRAIL.

Amino Acid Sequence↗
PubMed2000

Nitric oxide modulates expression of cell cycle regulatory proteins: a cytostatic strategy for inhibition of human vascular smooth muscle cell proliferation.

BACKGROUND: We examined the effect of NO on the proliferation and cell cycle regulation of human aortic vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: The NO donor diethylenetriamineNONOate (10(-5) to 10(-3) mol/L) inhibited proliferation in response to 10% fetal calf serum (FCS) and 100 ng/mL platelet-derived growth factor-BB in a concentration-dependent manner. This effect was not observed with disintegrated diethylenetriamineNONOate or with the parent compound, diethylenetriamine. Adenoviral transfection of endothelial NO synthase (NOS) inhibited proliferation in response to FCS, which was prevented with N(G)-nitro-L-arginine methyl ester. NOS overexpression did not inhibit proliferation in response to platelet-derived growth factor, although the transfection efficiency and protein expression were similar to those of FCS-stimulated cells. Nitrate release was selectively enhanced from FCS-treated cells, indicating that NOS was activated by FCS only. NO caused G(1) cell cycle arrest. Cytotoxicity was determined with trypan blue exclusion, and apoptosis was assessed with DNA fragmentation. Cyclin-dependent kinase 2 expression level, threonine phosphorylation, and kinase activity were inhibited. Cyclin A expression was blunted, whereas cyclin E remained unchanged. p21 expression was induced, and p27 remained unaltered. The effect on cyclin A and p21 started within 6 hours and preceded the changes in cell cycle distribution. Proliferation in response to 10% FCS was barely inhibited with 8-bromo-cGMP (10(-3) mol/L) but was blunted with both forskolin and 8-bromo-cAMP. Proliferation in response to 2% FCS was inhibited with 8-bromo-cGMP, but it did not mimic the cell cycle effects of NO. CONCLUSIONS: NO inhibits VSMC proliferation by specifically changing the expression and activity of cell cycle regulatory proteins, which may occur independent of cGMP. Adenoviral overexpression of endothelial NOS represents a cytostatic strategy for gene therapy of vascular disease.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

The Drosophila caspase DRONC is regulated by DIAP1.

We have isolated the recently identified Drosophila caspase DRONC through its interaction with the effector caspase drICE. Ectopic expression of DRONC induces cell death in Schizosaccharomyces pombe, mammalian fibroblasts and the developing Drosophila eye. The caspase inhibitor p35 fails to rescue DRONC-induced cell death in vivo and is not cleaved by DRONC in vitro, making DRONC the first identified p35-resistant caspase. The DRONC pro-domain interacts with Drosphila inhibitor of apoptosis protein 1 (DIAP1), and co-expression of DIAP1 in the developing Drosophila eye completely reverts the eye ablation phenotype induced by pro-DRONC expression. In contrast, DIAP1 fails to rescue eye ablation induced by DRONC lacking the pro-domain, indicating that interaction of DIAP1 with the pro-domain of DRONC is required for suppression of DRONC-mediated cell death. Heterozygosity at the diap1 locus enhances the pro-DRONC eye phenotype, consistent with a role for endogenous DIAP1 in suppression of DRONC activation. Both heterozygosity at the dronc locus and expression of dominant-negative DRONC mutants suppress the eye phenotype caused by reaper (RPR) and head involution defective (HID), consistent with the idea that DRONC functions in the RPR and HID pathway.

Animals↗
PubMed2000

alpha-t-butyl- and alpha-i-propyl-ortho-hydroxybenzylamines: racemic synthesis/resolution and asymmetric synthesis.

Efficient routes to alpha-tert-butyl- and alpha-iso-propyl-ortho-hydroxybenzylamines 1a and 1b are described. Highly enantioenriched 1a and 1b were obtained by resolution of the methoxy derivatives 2 by recrystallization of the salts formed with mandelic acid followed by Lewis acid mediated demethylation. The chiral 1,3-amino alcohol 1a has also been obtained in an asymmetric synthesis with the key step a diastereoselective alkylation of the imine obtained by condensation of o-anisaldehyde with phenyl glycinol. The absolute stereochemistry of these 1,3-aminophenols was determined by CD spectroscopy of the salicylideneamines 12 and by an X-ray structure analysis of the salt formed between (R)-mandelic acid and (S)-alpha-tert-butyl-ortho-methoxybenzylamine ((S)-2a).

Journal Article↗