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1.
By introducing replicate observations into observer agreement studies, one can obtain better measures of observer agreement than heretofore possible. New methodology based on the analysis of latent variables allows a separation of within- and between-observer variation for binary measures of assessment among pairs of observers. Maximum likelihood estimation and hypothesis testing are discussed. The methodology is illustrated using data on the assessment of dysplasia by pathologists. 相似文献
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Jha A Mukherjee C Prasad AK Parmar VS Clercq ED Balzarini J Stables JP Manavathu EK Shrivastav A Sharma RK Nienaber KH Zello GA Dimmock JR 《Bioorganic & medicinal chemistry》2007,15(17):5854-5865
A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC(50) figures were submicromolar and lower than melphalan. Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan. Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 microM. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice. 相似文献
5.
The effect of microbial enzymes in reducing the disposable solid content of sludge was investigated. A mixture of industrial
cellulase, protease, and lipase, in equal proportion by weight, reduced total suspended solids (TSS) by 30–50% and improved
settling of solids. An increase in solid reduction was observed with increasing enzyme concentration. The effect of combinations
of enzyme treatments indicated that two-enzyme combinations of protease and cellulase produced better solid reduction than
individual enzymes and that lipase further augmented this effect. Among the individual enzymes, protease produced a more settleable
sludge as compared to cellulase and lipase. Adjustment of the pH of the enzymatically treated sludge to the acidic range (pH
2–4) further improved solid reduction, and adjustment to the alkaline range (pH 10–12) improved settleability. Journal of Industrial Microbiology & Biotechnology (2001) 26, 383–386.
Received 01 November 2000/ Accepted in revised form 29 April 2001 相似文献
6.
An investigation on the effects of four different concentrations of peel extract from Citrus sinensis (CS) or Punica granatum (PG) in male mice revealed the maximum glucose lowering and antiperoxidative activities at 25 mg/kg of CS and 200 mg/kg of PG. In a separate experiment their potential was evaluated with respect to the regulation of alloxan induced diabetes mellitus. While a single dose of alloxan (120 mg/kg) increased the serum levels of glucose and alpha-amylase activity, rate of water consumption and lipid peroxidation (LPO) in hepatic, cardiac and renal tissues with a parallel decrease in serum insulin level, administration of 25 mg/kg of CS or 200 mg/kg of PG was found to normalize all the adverse changes induced by alloxan, revealing the antidiabetic and anti peroxidative potential of test fruit peel extracts. Subsequent phytochemical analysis indicated that the high content of total polyphenols in the test peels might be related to the antidiabetic and antiperoxidative effects of the test peels. 相似文献
7.
Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis 总被引:1,自引:0,他引:1
Group B and C Neisseria meningitidis are the major cause of meningococcal
disease in the United States and in Europe. N . meningitidis
lipooligosaccharide (LOS), a major surface antigen, can be divided into 12
immunotypes of which L1 through L8 were found among Group B and C
organisms. Groups B and C but not Group A may sialylate their LOSs with
N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they
synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as
probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4,
L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis
leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc
sequence, but not to Sambucus nigra agglutinin, which binds
NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot
analyses revealed that these six LOSs contained only the
NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS
components, which have a common terminal lacto-N-neotetraose (LNnT,
Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown
by previous studies. The LOS-lectin binding was abolished when the LOSs
were treated with Newcastle disease viral neuraminidase which cleaves
alpha2-->3 linked sialic acid. Methylation analysis of a representative
LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs
structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide)
and sialylparagloboside and some glycoproteins in having LNnT and
N-acetyllactosamine sequences, respectively, with or without alpha2-->3
linked NeuNAc. The molecular mimicry of the LOSs may play a role in the
pathogenesis of N.meningitidis by assisting the organism to evade host
immune defenses in man.
相似文献
8.
BRASSICA NAPUS was grown under hydroponic conditions and responses to the removal of the external supply of sulfur (S) were analysed in roots and in leaves of different developmental age. The concentrations of sulfate and nitrate were greatest in the older leaves and least in younger leaves, whilst phosphate was greatest in roots and youngest leaves and least in old leaves. S-deprivation resulted in decreases in tissue sulfate concentrations at variable rates in the order: roots and young leaves > middle-aged leaves > oldest leaves. Phosphate concentrations were unaffected and nitrate concentrations were only depleted in the oldest leaves. Expression of representative members of the sulfate transporter gene family was assessed by Northern blotting in the respective tissues. Group 1 transporters (high affinity type) were induced in response to S-deprivation in all tissues except old leaves, where no expression was detected, and to the greatest extent in roots. Groups 2 and 5 (a BRASSICA Group 5 sulfate transporter is reported here, accession number: AJ311389) transporters showed either no or only a small induction by S-deprivation. Group 4 transporters (localised in the tonoplast membrane and thought to be involved in vacuolar sulfate efflux) were induced by S-deprivation with a complex pattern: 4;1 was expressed in root and mature leaves, was strongly induced by sulfur-deprivation in roots, and was also induced in the middle-aged leaves alone; 4;2 was only expressed under S-deprivation in parallel with the observed pattern of tissue sulfate concentrations. Expression patterns indicated that both differences in intracellular sulfate pools and localised aspects of the signal transduction pathway link tissue sulfate-status and sulfur-nutrition regulated gene expression. 相似文献
9.
Lotta Kilpinen Feven Tigistu-Sahle Sofia Oja Dario Greco Amarjit Parmar P?ivi Saavalainen Janne Nikkil? Matti Korhonen Petri Lehenkari Reijo K?kel? Saara Laitinen 《Journal of lipid research》2013,54(3):622-635
Human mesenchymal stem/stromal cells (hMSC) are increasingly used in advanced cellular therapies. The clinical use of hMSCs demands sequential cell expansions. As it is well established that membrane glycerophospholipids (GPL) provide precursors for signaling lipids that modulate cellular functions, we studied the effect of the donor''s age and cell doublings on the GPL profile of human bone marrow MSC (hBMSC). The hBMSCs, which were harvested from five young and five old adults, showed clear compositional changes during expansion seen at the level of lipid classes, lipid species, and acyl chains. The ratio of phosphatidylinositol to phosphatidylserine increased toward the late-passage samples. Furthermore, 20:4n-6-containing species of phosphatidylcholine and phosphatidylethanolamine accumulated while the species containing monounsaturated fatty acids (FA) decreased during passaging. Additionally, in the total FA pool of the cells, 20:4n-6 increased, which happened at the expense of n-3 polyunsaturated FAs, especially 22:6n-3. The GPL and FA correlated with the decreased immunosuppressive capacity of hBMSCs during expansion. Our observations were further supported by alterations in the gene expression levels of several enzymes involved in lipid metabolism and immunomodulation. The results show that extensive expansion of hBMSCs harmfully modulates membrane GPLs, affecting lipid signaling and eventually impairing functionality. 相似文献
10.
Paroo Narsi Parmar Charles Alistair Brearley 《The Plant journal : for cell and molecular biology》1993,4(2):255-263
Components of the polyphosphoinositide signalling pathway have been identified in stomatal guard cells of Commelina communis L., one of the few plant systems shown unequivocally to be capable of responding to release of inositol 1,4,5-trisphosphate in the cytoplasm by increase in cytoplasmic Ca2+ . 'Isolated' epidermal strips of C. communis (in which all cells other than guard cells have been killed by treatment at low pH) were radiolabelled with myo -[2n-3 H]inositol or [32 P]orthophosphate for 17–18 h. The phosphoinositides and inositol phosphates were extracted. Phosphoinositides were deacylated and the head groups resolved by HPLC. The water-soluble products generated by mild periodate cleavage of HPLC-purified, deacylated lipid fractions were examined. The resulting biochemical analysis led to the identification of: PtdIns, PtdIns3 P , PtdIns4 P , PtdIns(3,4) P 2 and PtdIns(4,5) P 2 . Thex inositol phosphates were resolved by HPLC. Preliminary analysis of HPLC-purified putative inositol phosphate fractions resulted in the identification of each inositol phosphate class, that is, Ins P , Ins P 2 , Ins P 3 , Ins P 4 , Ins P 5 and InsP 6 . Many of these inositol phosphates occurred in different isomeric forms. The presence of 3-phosphorylated phosphoinositides suggests that they may have a role in signalling in stomatal guard cells. 相似文献