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41.
42.
Ferraris D Ko YS Calvin D Chiou T Lautar S Thomas B Wozniak K Rojas C Kalish V Belyakov S 《Bioorganic & medicinal chemistry letters》2004,14(22):5579-5583
In this paper, the synthesis and structure-activity relationships (SAR) of two classes of electrophile-based dipeptidyl peptidase IV (DPP IV) inhibitors, the ketopyrrolidines and ketoazetidines, is discussed. The SAR of these series demonstrate that the 2-thiazole, 2-benzothiazole, and 2-pyridylketones are optimal S1' binding groups for potency against DPP IV. In addition, both cyclohexyl glycine (CHG) and octahydroindole carboxylate (OIC) serve as the most potent S2 binding groups within each series. Stereochemistry at the alpha-position of the central ring is relevant to potency within the ketopyrrolidines series, but not in the ketoazetidine series. Finally, the ketoazetidines display enhanced stability over the corresponding ketopyrrolidines, while maintaining their potency. In fact, certain stabilized ketoazetidines can maintain their in vitro potency and inhibit DPP IV in the plasma for up to 6h. 相似文献
43.
Only neutral polymorphisms found in the TIGR/myocilin gene of 45 Polish patients with primary open-angle glaucoma 总被引:1,自引:0,他引:1
Krawczyński MR Czarny-Ratajczak M Pecold K Latos-Bieleńska A 《Journal of applied genetics》2004,45(2):275-279
The aim of the study was to identify mutations of the TIGR gene in Polish patients with primary open-angle glaucoma (POAG) and to define possible genotype-phenotype correlations. The study included 45 patients with a verified diagnosis of POAG. The PCR amplification of all three exons of the TIGR gene and screening for the sequence changes by CSGE analysis was done for every patient. The probes with identified heteroduplexes were sequenced. Altogether 315 PCR products were obtained. The CSGE analysis detected 60 possible changes of the sequence in 28 patients. 34 heteroduplexes were chosen for sequencing, including 29 unique changes and 5 changes representative of identical heteroduplexes. Direct sequencing enabled detection of only four different changes in the TIGR gene sequence. Three of them: 5'UTR -83G-->A (in 14 patients), +227 exon 1 G-->A, Arg76Lys (in 14 patients) and +311 exon 3 T-->C, Tyr347Tyr (in 4 patients) have already been described in the literature as neutral polymorphisms of the gene. Only one change in the promoter, 5'UTR -126T-->C (in 2 patients), has not been described in the literature to date. However, this change does not alter directly the sequence of amino acids in myocilin, so it is difficult to conclude on its pathogenetic role. Thus our study showed only neutral polymorphisms of the TIGR gene. This suggests that the patients probably have mutations in other genes, so other loci that predispose to POAG must be analyzed. 相似文献
44.
Chechlińska M Duma A Swierkowska K Kamińska J Steffen J 《Cellular & molecular biology letters》2004,9(1):69-81
We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Ralpha and inhibiting the release of IL-1beta and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients' blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Ralpha in the effects observed. 相似文献
45.
Qualitative and quantitative composition of pigments in Phaeodactylum tricornutum (Bacillariophyceae) stressed by iron 总被引:1,自引:0,他引:1
The effect of Fe(III) deficiency on qualitative and quantitative changes in pigment composition in Phaeodactylum tricornutum Bohlin was demonstrated by HPLC and AAS. Maximum content of pigments showed the diatom cells incubated at the optimum iron concentration, i.e., 10 M. The contents of chlorophyll a, chlorophyll c
1+c
2, fucoxanthin, diadinoxanthin and ,-carotene were 109.99, 20.16, 40.39, 1.29 and 1.48 fg per cell, respectively. The results obtained showed that Fe(III) affected qualitative and quantitative pigment composition in P. tricornutum. The content of individual pigments, proportions between accompanying pigments and their ratios to chlorophyll a were important indicators of phytoplankton response to iron stress. The strong reduction in ,-carotene content, several times (2–5) increase in diadinoxanthin level as compared to ,-carotene, and high amount of diadinoxanthin in relation to chlorophyll a were observed in algae growing at very low Fe(III) concentrations, 0.001 and 0.01 M. The data suggested that phytoplankton pigments could be a potential physiological marker. 相似文献
46.
M.?A.?Shatnawi K.?A.?JohnsonEmail author 《In vitro cellular & developmental biology. Plant》2004,40(2):239-244
Summary Christmas bush (Ceratopetalum gummiferum Sm) is a shrubby tree species of the east coast of New South Wales in Australia. It is much prized as a cut flower crop because
of its bright, pinky red floral calyces. New varieties are being developed, the storage of which is an important issue. In
this study, it was shown that shoot tips sampled from in vitro plantlets withstood cryopreservation using the encapsulation-dehydration technique. The protocol leading to optimal regrowth
was the following: excised shoot tips were pretreated for 1 d in the dark on hormone-free Murashige and Skoog (MS) medium
with 0.3 M sucrose, then encapsulated in 3% calcium alginate and precultured in liquid MS medium with 0.5 M sucrose for 3 d. Precultured beads were dehydrated for 6 h in the air current of the laminar flow cabinet to 24.3% moisture
content (fresh weight basis) before rapid immersion in liquid nitrogen. Under these conditions, regrowth of shoot tips after
cryopreservation reached 61.4%. Regrowth of cryopreserved shoot tips was not affected by the period of cold acclimation of
in vitro mother plants. 相似文献
47.
M.?Awad?Shatnawi Krystyna?A.?JohnsonEmail author Fraser?R.?Torpy 《In vitro cellular & developmental biology. Plant》2004,40(4):403-407
Summary An efficient procedure for the in vitro propagation and cryogenic conservation of Syzygium francissi was developed. The maximum number of shoots per explant was obtained on a Murashige and Skoog (MS) medium supplemented with
4.5 μM benzyladenine and 0.5 μM indole-3-butyric acid (IBA). The in vitro-propagated shoots produced roots when transferred to MS medium containing IBA, indold-3-acetic acid, or naphthaleneacetic
acid at various concentrations. Rooted microshoots were transferred to a coco-peat, perlite, and vermiculite (1∶1∶1) mixture,
and hardened off under greenhouse conditions. Ninety-five percent of rooted shoots successfully acclimatized in the greenhouse.
Shoot tips excised from in vitro-grown plants were successfully cryostoraged at −196°C by the encapsulation-dehydration method. A preculture of formed beads
on MS medium containing 0.75 M sucrose for 1 d, followed by 6 h dehydration (20% moisture content) led to the highest survival rate after cryostorage for
1h. This method is a promising technique for in vitro propagation and cryopreservation of shoot tips from in vitro-grown plantlets of S. francissi germplasm. 相似文献
48.
Virus-neutralizing activity mediated by the Fab fragment of a hemagglutinin-specific antibody is sufficient for the resolution of influenza virus infection in SCID mice 下载免费PDF全文
Antibodies (Abs) contribute to the control of influenza virus infection in vivo by reducing progeny virus yield from infected cells (yield reduction [YR]) and by inhibiting progeny virus from spreading the infection to new host cells (virus neutralization [VN]). Previous studies showed that the infection could be resolved in severe combined immunodeficiency (SCID) mice by treatment with hemagglutinin (HA)-specific monoclonal antibodies (MAbs) that exhibit both VN and YR activities but not by MAbs that exhibited only YR activity. To determine whether virus clearance requires both activities, we measured the therapeutic activity of an HA-specific MAb (VN and YR) and its Fab fragment (VN) by intranasal (i.n.) administration to infected SCID mice. Immunoglobulin G (IgG) and Fab cleared the infection with i.n. 50% effective doses (ED(50)s) of 16 and 90 pmol, respectively. To resolve an established infection solely by VN activity, Fab must be present in the respiratory tract at an effective threshold concentration until all infected cells have died and production of virus has ceased. Because IgG and Fab had different half-lives in the respiratory tract (22 and 8 h, respectively) and assuming that both operated mainly or solely by VN, it could be estimated that clearance was achieved 24 h after Ab treatment when both reagents were present in the respiratory tract at approximately 10 pmol. This dose was approximately 200 times larger than the respiratory tract-associated Ab dose resulting from administration of the intraperitoneal ED(50) (270 pmol) of IgG. This indicated that our procedure of i.n. administration of Ab did not make optimal use of the Ab's therapeutic activity. 相似文献
49.
Golabek AA Kida E Walus M Wujek P Mehta P Wisniewski KE 《The Journal of biological chemistry》2003,278(9):7135-7145
Human tripeptidyl-peptidase I (TPP I, CLN2 protein) is a lysosomal serine protease that removes tripeptides from the free N termini of small polypeptides and also shows a minor endoprotease activity. Due to various naturally occurring mutations, an inherited deficiency of TPP I activity causes a fatal lysosomal storage disorder, classic late infantile neuronal ceroid lipofuscinosis (CLN2). In the present study, we analyzed biosynthesis, glycosylation, transport, and proteolytic processing of this enzyme in stably transfected Chinese hamster ovary cells as well as maturation of the endocytosed proenzyme in CLN2 lymphoblasts, fibroblasts, and N2a cells. Human TPP I was initially identified as a single precursor polypeptide of approximately 68 kDa, which, within a few hours, was converted to the mature enzyme of approximately 48 kDa. Compounds affecting the pH of intracellular acidic compartments, those interfering with the intracellular vesicular transport as well as inhibition of the fusion between late endosomes and lysosomes by temperature block or 3-methyladenine, hampered the conversion of TPP I proenzyme into the mature form, suggesting that this process takes place in lysosomal compartments. Digestion of immunoprecipitated TPP I proenzyme with both N-glycosidase F and endoglycosidase H as well as treatment of the cells with tunicamycin reduced the molecular mass of TPP I proenzyme by approximately 10 kDa, which indicates that all five potential N-glycosylation sites in TPP I are utilized. Mature TPP I was found to be partially resistant to endo H treatment; thus, some of its N-linked oligosaccharides are of the complex/hybrid type. Analysis of the effect of various classes of protease inhibitors and mutation of the active site Ser(475) on human TPP I maturation in cultured cells demonstrated that although TPP I zymogen is capable of autoactivation in vitro, a serine protease that is sensitive to AEBSF participates in processing of the proenzyme to the mature, active form in vivo. 相似文献
50.
Hendrich AB Wesołowska O Motohashi N Molnár J Michalak K 《Biochemical and biophysical research communications》2003,304(2):260-265
The phenothiazine multidrug resistance (MDR) modulators are chemically diversified but share the common feature to be hydrophobic cationic molecules. Molecular mechanisms of their action may involve interactions with either P-glycoprotein or membrane lipid matrix. In the present work we study the anti-MDR and biophysical membrane effects of new phenothiazine derivatives differing in the type of group substituting phenothiazine ring at position 2 (H-, Cl-, CF(3)-) and in the side chain group (NHCO(2)CH(3) or NHSO(2)CH(3)). Within each phenothiazine subset we found that anti-MDR activity (determined by P-glycoprotein inhibition assessed by flow cytometry) correlates with the theoretically calculated hydrophobicity value (logP) and experimental parameters (determined by calorimetry and fluorescence spectroscopy) of lipid bilayers. It is concluded that the biological and biophysical activity of phenothiazine derivatives depends more on the type of ring substitution than on the nature of the side chain group. 相似文献