Economic realities of faculty practice.
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Biomedical subjects
Publications and source records attributed to J Jezek.
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The immunoadjuvant activity of muramyl dipeptide seems to be critically dependent on the type of substitution of the gamma-carboxyl group of the D-isoglutamine residue. Moreover the nonapeptide L-Ala-D-isoGlu-L-lys-D-Ala-(Gly)5-OME also shows a definite effect.
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In 20, 40 and 60-day-old rats the filtration rate was studied using Baines modification of Hanssen's Na4Fe (14CN)6 method enabeling the determination of single nephron glomerular filtration rate (SNGFR) ratio between superficial (S), intercortical (I) and juxtamedullary (J) nephrons. The proximal tubule lengths were determined as well. A close correlation was obtained between age and S/I, I/J and S/J of proximal tubule lengths and between age and I/J, S/J 14C-activities of ferro-cyanide. Presented findings confirm the data on the increasing role of superficial nephrons in the course of postnatal development of rat.
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Protection from undesirable effects of radiotherapy or chemotherapy, primarily from myelosuppression, remains still a crucial problem to be studied. Attention has been therefore paid to various immunomodulatory agents that through the monocyte/macrophage system induced production of cytokines, which can induce and operate restoration of haemopoiesis and thus act radioprotectively. Some synthetic analogues of MDP free of undesirable side-effects, were synthesized in the Czech Republic. Lipophilic beta-D-GlcNstearoyl-(1- > 4)-norMurNAc-L-Abu-D-isoGln (DDD-St) was designed to be easily entrapped into liposomes and this liposomal DDD-St protected efficiently mice against irradiation, when administered i.p., i.v. or s.c. 24 h prior to lethal irradiation (survival rate in the range of 30-80% compared with 0% in control). Especially the subcutaneous application of liposomal DDD-St was very efficient. The parameters characteristic of recovery of haemopoiesis in bone marrow on day 10 after 6.5 Gy irradiation were significantly improved in comparison with the controls. Very high radioprotective effect of s.c. administered liposomal DDD-St can be explained (together with induction of haemopoiesis) by an effective and long-lasting activation of nonspecific immunity, which is able to withhold an onset of septicemia in early days after irradiation. In conclusion, the liposomal DDD-St should be therapeutically beneficial in moderating the haemopoietic damage, which is an undesirable effect of radiotherapy or chemotherapy.
Two different approaches to the interrogation of prokaryotic and eukaryotic cells have been explored, with the objective of developing biosensor based rapid ecotoxicity test protocols for use in a wide range of applications. Prokaryotic cells and some eukaryotic cell types lend themselves to interrogation by mediated amperometry, a technique that allows metabolic activity of the cell to be monitored by accessing cellular redox events with a chemical mediator. Reduction of the mediator by the cell is followed by re-oxidation at an electrode surface poised at a fixed potential. The resulting current flow is proportional to the metabolic status of the cell. A commercial ecotoxicity test, CellSense, employing such whole cell biosensors has now been developed. An alternative approach to interrogation of vertebrate cells has been the use of luminescent reporter genes to determine changes in the metabolic status of the cells following environmental challenge. Several clones have been established of epithelial cells from the bluegill sunfish (BF-2), transfected with the pCIneoLuc plasmid, that express luciferase constitutively. Protocols using these transformed cells are being developed to provide an alternative to the standard neutral red retention test.
Parallel simultaneous synthesis of fifty linear peptides has been carried out in order to compare in detail two promising methodologies of simultaneous multiple peptide synthesis (SMPS): the "T bag" method, utilizing 4-methyl-benzhydrylamine resin (MeBHA), and synthesis on derivatized Fmoc-Gly-O-cotton fabric strips. The basic set of experiments, which utilizes identical Fmoc/Bu(t) strategy for both approaches, shows that the peptides synthesized on cotton are superior in purity to those synthesized using T bags. In experiments utilizing Boc/Bzl strategy in T bags, the purities of peptides were higher than in the case of peptides synthesized in T bags by Fmoc/Bu(t) strategy, and comparable with the purities achieved in synthesis performed on cotton. The lower yields on cotton are caused by mechanical losses in the given experimental arrangement.
With the aim of synthesizing cyclic antagonists of the nonapeptide hormone bradykinin with minimal side chain modification, we performed backbone to backbone and backbone to side chain cyclization. To probe and compare different strategies for this new kind of cyclization, the branched peptide bonds were formed by both reductive alkylation on the solid phase and by using preformed building units. Lactam bridges between the modified amide groups were formed by the use of the phenylalanine derivatives N(CH2COOH)Phe and N(CH2CH2NH2)Phe. The best results in the formation of the N-alkylamide bond were obtained with the coupling reagent PyBrop. The coupling rate was monitored by estimation of the N-terminal Fmoc-group. The cyclization was performed on the solid support. Unexpected difficulties resulted from the instability of the N-alkylamide bond under strong acidic conditions, as used for deprotection and for removal from the resin. We synthesized peptides with backbone to backbone cyclization between positions 2 and 5, as well as backbone to side chain cyclizations between positions 0 and 5, and between 2 and 6. The relatively high biological activities of some of the cyclic analogues support the supposed receptor-bound conformation of bradykinin antagonists with a beta-turn in the N-terminal sequence.