Biomedical subjects

S Pallas

Publications and source records attributed to S Pallas.

4 recordsLinked to original sources

PubMed2001

Directed evolution and Phenomics screening of new biocatalysts.

Biodiversity screening and directed evolution are two fruitful complementary approaches for the discovery and design of novel biocatalysts. A new technology for directed evolution, L-Shuffling, has been designed and patented by Proteus. L-Shuffling technology offers several competitive advantages over other technologies including (i) directed evolution of large genes: L-Shuffling" means "Large-Shuffling"; (ii) high fidelity recombination and (iii) Control over location and frequency of recombination. The thousands of new recombinants generated by L-Shuffling can be further screened for their biochemical characteristics using Phenomics. Phenomics is a proprietary functional HTS technology designed and patented by Proteus for the screening of natural biodiversity as well as biodiversity generated by combinatorial biology. Phenomics is a function to gene structure approach which provides an alternative to genomics and proteomics. The traditional limits of expression libraries are thereby circumvented especially those related to cytotoxic products in usual or specific surrogate hosts. The quality of the answer given by the screening is directed dependent on the quality of the question asked. Thanks to a new substrates synthesis technology named CLIPS-O, the company can design highly specific molecules simulating the chemical structure and energetic state of the industrial substrates. The whole process of novel biocatalysts discovery has been automated using commercially available high throughput robotics.

Bacteria↗

PubMed1992

Scotopic versus photopic pattern onset-offset electroretinograms.

We investigated the contribution of rods and cones to the human pattern electroretinogram to onset and offset checkerboards of different spatial frequency and wavelength in a 39 degrees x 39 degrees field. Under strictly scotopic conditions, there was a negative potential at onset and a positive potential at offset, whereas under photopic conditions, there was a positive potential at onset and a negative/positive potential at offset. Thus, the waveform to pattern onset (offset) was that of the luminance electroretinogram to decreasing (increasing) luminances. For pattern onset, the sensitivity difference 486-601 nm under scotopic and photopic conditions closely followed the luminosity function of rods and cones. The amplitude of the scotopic onset response increased with check size up to 3 degrees 30' and that of the photopic onset response, up to 30'. With larger checks, the scotopic and photopic onset response markedly decreased. This indicates antagonistic center-surround organization of the receptive fields under both scotopic and photopic conditions. By contrast, the offset response monotonically increased with check size under scotopic and photopic conditions, which suggests a luminance component in the pattern electroretinogram. Consequently, the pattern electroretinogram to reversing checkerboards has to be regarded as a mixture of both pattern- (contrast) and luminance-specific components.

Adolescent↗

PubMed1989

M2 muscarinic receptors on the iris sphincter muscle differ from those on iris noradrenergic nerves.

The pre- and postjunctional affinity constants of a series of muscarinic antagonists were determined in guinea pig and rabbit irises. Field stimulation-evoked [3H]noradrenaline release from superfused isolated irises was concentration dependently inhibited by (+/-)-methacholine, confirming the presence on the iris noradrenergic nerves of prejunctional inhibitory muscarinic receptors. The affinity constants of the antagonists at the pre- and postjunctional receptors are compatible with the coexistence in the iris of two different M2 receptors: the cardiac (M2 alpha) subtype on the noradrenergic nerves and the smooth muscle (M2 beta) subtype on the iris sphincter muscle. The rank order of potency of the antagonists studied at the prejunctional site was: atropine greater than himbacine greater than AF-DX 116 greater than pirenzepine greater than hexahydrosiladifenidol. The order of potency at the postjunctional receptors mediating the methacholine-induced isotonic contraction of the isolated rabbit iris sphincter was: atropine greater than hexahydrosiladifenidol greater than pirenzepine greater than himbacine greater than AF-DX 116.

Animals↗

PubMed1988

Muscarinic inhibition of [3H]-noradrenaline release on rabbit iris in vitro: effects of stimulation conditions on intrinsic activity of methacholine and pilocarpine.

1. Rabbit isolated irides were loaded with [3H]-noradrenaline and superfused with Tyrode solution. The inhibition by the muscarinic agonists (+/-)-methacholine and pilocarpine of the [3H]-noradrenaline overflow into the superfusate evoked by field stimulation (pulses of 1 ms duration, 75 mA) was measured as an index of activation of presynaptic muscarinic receptors. 2. The fractional rate of release per pulse during the first stimulation period (S1) was low with 360 pulses at 3 Hz, intermediate with 360 pulses at 10 Hz and high with 1200 pulses at 10 Hz. Upon repetitive stimulation (7 periods at 20 min intervals), the fractional rates of release per pulse during S7 no longer differed, suggesting a 'long-term' regulation of [3H]-noradrenaline release depending on the stimulation conditions. 3. The evoked [3H]-noradrenaline overflow was depressed by (+/-)-methacholine in a concentration-dependent manner. The EC50 ranged from 0.29 to 0.42 microM. Methacholine nearly abolished the transmitter release evoked at 3 Hz but reduced that induced at 10 Hz by only 50%. Under the latter condition the methacholine concentration-inhibition curve was bell-shaped and no muscarinic inhibition was observed in the presence of methacholine 30 microM. After washout of methacholine the evoked [3H]-noradrenaline release was temporarily enhanced. 4. Atropine 0.1 microM enhanced the [3H]-noradrenaline overflow (evoked by stimulation with 360 or 1200 pulses at 10 Hz), probably antagonizing a presynaptic inhibition by endogenous acetylcholine. The inhibition by methacholine was competitively antagonized by atropine 0.1 microM (apparent -log KB = 8.5-9.0). 5. Depending on the concentration, pilocarpine reduced the [3H]-noradrenaline overflow evoked by 360 pulses at 3 Hz up to 63%. However, at 10 Hz stimulation frequency the compound was inactive as an agonist but competitively antagonized the presynaptic inhibition induced by methacholine. The KB under the latter condition (0.95 microM) was very close to the EC50 value determined at 3 Hz (0.85 microM). 6. The results demonstrate a muscarinic inhibition of noradrenaline release from the rabbit isolated iris. The activation by pilocarpine of the presynaptic receptors provides an alternative explanation for the miosis induced in the rabbit in vivo, which might be the result of a decreased sympathetic tone in the iris dilator muscle.

Animals↗