Do advanced glycation end products and glucose induce similar signaling events in mesangial cells?
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8-Hydroxy-2'-Deoxyguanosine↗
Biomedical subjects
S K Biswas
Publications and source records attributed to S K Biswas.
Thermal study of accumulation of conformational disorders in the self-assembled monolayers of C8 and C18 alkanethiols on the Au111 surface.
The thermal stability of short alkanethiol CH(3)(CH(2))(7)SH (C(8)) and long C(18) self-assembled monolayers (SAMs) is investigated using grazing angle reflection-absorption infrared spectroscopy, cyclic voltammetry, and molecular dynamics simulation. We track the disordering of SAM by untilting and gauche defect accumulation with increasing temperature in the 300-440 K range, a range of interest to tribology. Molecular dynamics simulation with both fully covered and partially covered C(6), C(8), and C(18) monolayers brings out the morphological changes in the SAM, which may be associated with the observed thermal stability characteristics. The molecular dynamics simulations reveal that short-chain C(6) and C(8) alkanethiols are more defective at lower temperature than the long-chain C(18) alkanethiol. With increasing temperature disorder in the SAM, as reflected in both untilting and gauche defect accumulation, tends to saturate at temperatures below 360 K for short-chain SAMs such that any further increase in temperature, until desorption, does not lead to any significant change in conformational order. In contrast the disorder in the long-chain C(18) SAM increases monotonically with temperature beyond 360 K. Thus, in a practical range of temperature, the ability of a SAM to retain order with increasing thermal perturbations is governed by the state of disorder prior to heat treatment. This deduction derived from molecular dynamics simulation helps to rationalize the significant difference we have observed experimentally between the thermal response of short- and long-chain thiol molecules.
Journal Article↗
Davis BJ, Forbes JM, Thomas MC et al. (2004) Superior renoprotective effects of combination therapy with ACE and AGE inhibition in the diabetic spontaneously hypertensive rat. Diabetologia 47:89-97.
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Angiotensin-Converting Enzyme Inhibitors↗
Thermal stability of perfluoroalkyl silane self-assembled on a polycrystalline aluminum surface.
Thermal stability behavior of 1H, 1H,2H,2H-perfluorooctyl trichlorosilane self-assembled on aluminum substrates is characterized using a grazing-angle Fourier transform infrared spectrometer, Fourier transform-Raman spectroscopy, and contact angle measurements. The self-assembled monolayer (SAM) is heated quasi-statically from room temperature to above 633 K with a heating rate of 1 K/s. Variations in peak frequencies, integrated areas of intensities of symmetric and antisymmetric CF2 stretches, and the relative tilt angle of the SAM are reported. We find that the conformational order in the SAM is not disrupted because of thermal cycling when the peak temperature is below 423 K. When the peak temperature is between 423 and 603 K, the cycling results in only a partial retention of the original order. When the peak temperature is above 603 K, the process is completely irreversible. Surface-enhanced Raman spectroscopy and contact angle measurements support these observations. We confirm these trends for a longer chain (1H,1H,2H,2H-perfluordecyl trichlorosilane) molecule of the same family using the same techniques. We discuss the possible reasons for the changes in light of the tilting-untilting and uncoiling-coiling of the helical silane monolayer.
Journal Article↗
-to: Gardiner TA, Anderson HR, Degenhardt T et al. (2003) prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug. Diabetologia 46:1269-1275.
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Animals↗
Regulation of nitric oxide production by murine peritoneal macrophages treated in vitro with chemokine monocyte chemoattractant protein 1.
Monocyte chemoattractant protein 1 (MCP-1) is an important mediator of monocyte/macrophage recruitment and activation at the sites of chronic inflammation and neoplasia. In the current study, the role of nitrogen monoxide (NO) in the activation of murine peritoneal macrophages to the tumoricidal state in response to in vitro MCP-1 treatment and the regulatory mechanisms involved therein were investigated. Murine peritoneal macrophages upon activation with MCP-1 showed a dose- and time-dependent production of NO together with increased tumoricidal activity against P815 mastocytoma cells. N-monomethyl-l-arginine (L-NMMA), a specific inhibitor of the l-arginine pathway, inhibited the MCP-1-induced NO secretion and generation of macrophage-mediated tumoricidal activity against P815 (NO-sensitive, TNF-resistant) cells but not the L929 (TNF-sensitive, NO-resistant) cells. These results indicated l-arginine-dependent production of NO to be one of the effector mechanisms contributing to the tumoricidal activity of MCP-1-treated macrophages. Supporting this fact, expression of iNOS mRNA was also detected in the murine peritoneal macrophages upon treatment with MCP-1. Investigating the signal transduction pathway responsible for the NO production by the MCP-1-activated murine peritoneal macrophages, it was observed that the pharmacological inhibitors wortmannin, H-7 (1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride), and PD98059 blocked the MCP-1-induced NO production, suggesting the probable involvement of phosphoinositol-3-kinase, protein kinase C, and p42/44 MAPkinases in the above process. Various modulators of calcium and calmodulin (CaM) such as EGTA, nifedipine, TMB-8 (3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester), A23187, and W-7 (N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide) were also found to modulate the in vitro macrophage NO release in response to MCP-1. This observation indicated the regulatory role of calcium/CaM in the process of MCP-1-induced macrophage NO production. Similarly, the role of serine/threonine and protein tyrosine phosphatases in the above pathway was suggested using the specific inhibitors of these phosphatases, okadaic acid and sodium orthovanadate.
Animals↗
Inhibition of hyphal growth of Candida albicans by activated lansoprazole, a novel benzimidazole proton pump inhibitor.
The effect of activated lansoprazole (AG 2000), a novel benzimidazole proton pump inhibitor, against hypha formation of Candida albicans was examined in hypha-forming medium pH 7 (HFM7) after 20 h. AG 2000, at 50-800 microM, did not inhibit germ tube formation. However, it inhibited elongation of germ tubes to form hyphae and favored conversion of germ tubes to resume yeast growth at concentrations of > or =200 microM. Pre-treatment of AG 2000 with a sulfhydryl reagent (1:1), such as 2-mercaptoethanol. blocked the inhibitory property of AG 2000 on hypha formation.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Molecular phylogenetics of the genus Rhodotorula and related basidiomycetous yeasts inferred from the mitochondrial cytochrome b gene.
Phylogenetic relationships of basidiomycetous yeasts, especially of the genus Rhodotorula, were studied using partial sequences of the mitochondrial cytochrome b gene. The results demonstrated that the basidiomycetous yeasts under investigation distributed into two main clusters: one containing Tremellales, Filobasidiales and their anamorphs and the other containing Ustilaginales, Sporidiales and their anamorphs. This clustering in turn correlates with cell wall biochemistry, presence or absence of xylose, and septal ultrastructure, dolipore or simple pore. Bullera, Bulleromyces, Filobasidiella, Cryptococcus and Trichosporon, yeasts of the former cluster, contain xylose in the cell wall and have dolipore septa. In contrast yeasts of the latter cluster, which included Bensingtonia, Erythrobasidium, Leucosporidium, Malassezia, Rhodosporidium, Rhodotorula, Sporidiobolus, Sporobolomyces and Ustilago, have no xylose in the cell wall and have a simple pore septum. Yeasts of the latter group could be further divided into four clades (A-D). Species of Rhodotorula were distributed in all of these clades, indicating the polyphyletic nature of the genus. A limited number of Rhodotorula species demonstrated identical sequences, for example Rhodotorula bacarum and Rhodotorula foliorum, Rhodotorula fujisanensis and Rhodotorula futronensis, Rhodotorula glutinis var. dairenensis and Rhodotorula mucilaginosa. However, all the other test species of the genus Rhodotorula were well separated based on their 396 bp nucleotide sequences. These results demonstrate the effectiveness of the use of cytochrome b sequences for both species identification and the study of phylogenetic relationships among basidiomycetous yeasts.
Amino Acid Sequence↗
Typing of Candida albicans isolates by sequence analysis of the cytochrome b gene and differentiation from Candida stellatoidea.
Including type strains, mitochondrial cytochrome b genes of 32 strains of Candida albicans and 6 strains of Candida stellatoidea, presently treated as a synonym for C. albicans, were partially sequenced. Analysis of 396-bp nucleotide sequences of the strains under investigation divided C. albicans isolates into three types: type I, type II, and type III; however, strains of C. stellatoidea represented distinct type IV isolates. Deduced amino acid sequences of type I, type II, and type III were identical and differed from that of type IV by one amino acid. Genotypes (rDNA type) of the test strains were also checked. Cytochrome b typing did not correlate with genotyping, and different genotypes occurred for one cytochrome b type. This study shows that cytochrome b gene sequences are useful for analyzing the genetic relatedness of C. albicans isolates and effective for differentiating C. stellatoidea from C. albicans.
Amino Acid Sequence↗
Identification of Candida dubliniensis based on the specific amplification of mitochondrial cytochrome b gene.
Candida dubliniensis, a recently described Candida species, is frequently isolated from oral candidiasis in human immunodeficiency virus infected individuals. To detect the organism rapidly, we have developed specific oligonucleotide primers based on the sequences of mitochondrial cytochrome b gene. These primers selectively amplified DNA only from C. dubliniensis; the DNAs of all pathogenic Candida species tested, as well as those of medically relevant yeasts such as Cryptococcus neoformans, and Trichosporon cutaneum, were not amplified. This is the first report describing the effectiveness of cytochrome b gene in PCR based detection of an organism, and we hope the system will be useful as a microbiological tool for rapid detection of C. dubliniensis.
Base Sequence↗
Glycaemic index of parboiled rice depends on the severity of processing: study in type 2 diabetic subjects.
OBJECTIVE: To study the influence of parboiling and the severity of the process on glycaemic and insulinaemic responses to rice in type 2 diabetes. Moreover, to examine changes in starch structure related to parboiling, which may affect the metabolic responses and digestibility. DESIGN: Nine type 2 diabetic subjects ingested four test meals: white bread (WB) and three meals of cooked polished rice of the same variety being non-parboiled (NP), mildly traditionally parboiled (TP) and severely pressure parboiled (PP). The participants ingested the test meals (50 g available carbohydrates) on separate occasions after an overnight fast. SETTING: Outpatient clinic, Dept. Endocrinology and Metabolism, Aarhus University Hospital, Denmark. RESULTS: All three rice samples elicited lower postprandial plasma glucose response (NP: 335+/-43; TP: 274+/-53; PP: 231+/-37 mmol/1*180 min.; means+/-s.e.m.) than white bread (626+/-80; P<0.001), within rice samples PP tended to be lower than NP (P=0.07). The glycaemic indices were: NP: 55+/-5, TP: 46+/-8 and PP: 39+/-6, and lower for PP than NP (P<0.05). The insulin responses were similar for the three rice meals, which were all lower than that to white bread (P<0.001). Differential scanning calorimetry showed the presence of amylose-lipid complexes in all rice samples and of retrograded amylopectin in PP. Amylose retrogradation was not detected in any of the rice samples. CONCLUSIONS: All rice test meals were low-glycaemic in type 2 diabetic subjects. There was no effect of TP on glycaemic index, whereas PP reduced the glycaemic index by almost 30% compared to NP. SPONSORSHIP: The Royal Veterinary and Agricultural University, Aarhus University Hospital, Danish International Development Assistance (DANIDA), Ministry of Foreign Affairs and the 'Konsul Johannes Fogh-Nielsens og Fru Ella Fogh-Nielsens Legat' foundation.
Aged↗
Effect of pH, carbon source and K+ on the Na+-inhibited germ tube formation of Candida albicans.
The effect of pH, carbon source and K+ on the Na+ -inhibited germ tube formation of the pathogenic fungus Candida albicans was examined in the arginine-phosphate modified (APM) medium. All C. albicans cells formed germ tubes in APM medium at pH 5.0-9.0. Na+ inhibited germ tube formation in a concentration dependent manner ranging from 0.2 to 1.0 M, and was further influenced by the pH of the medium. The inhibitory effect of Na+ was lowest at pH 8.0, and germ tube formation ceased at 1.0 M Na+ for any pH (4.0-9.0). At pH > or = 6.0, non-germ tube-forming cells did not show yeast growth; whereas at pH < or = 5.0, Na+ inhibited only germ tube formation but did not inhibit yeast growth. The inhibitory effect of Na+ was stronger in glucose medium than in galactose medium as carbon source. K+, at 0-0.8 M, had almost no effect on germ tube formation. However, in the presence of Na+, a very low concentration of K+ (0.5 mM) was able to release the cells from Na+ arrest and produced an increase in the rate as well as the percentage of germ tube formation. Intracellular Na+/K+ ratios increased with the increase in extracellular Na+ concentration, whereas the ratios decreased and remained within nontoxic levels when the extracellular K+ concentration was increased.
Candida albicans↗
Identification and phylogenetic relationship of the most common pathogenic Candida species inferred from mitochondrial cytochrome b gene sequences.
We sequenced a 396-bp region of the mitochondrial cytochrome b gene of the most common clinically important Candida species: Candida albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, and C. lusitaniae. The recently described species of Candida, C. dubliniensis, associated with mucosal candidiasis in human immunodeficiency virus-infected individuals, was also included. Two to five strains of each species were examined. Some species represented intraspecies variation, which was not more than 1.8% (DNA). However, interspecies variations were more than 10 and 7%, respectively, for DNA and amino acid sequences. Multiple alignments of nucleotide and deduced amino acid sequences revealed species-specific nucleotides and amino acids. Nucleotide- and amino acid-based phylogenetic trees were constructed and are discussed. Using the database, it is possible to identify presumptive Candida species within a working day.
Amino Acid Sequence↗
Efficacy of single-dose ROM therapy plus low-dose convit vaccine as an adjuvant for treatment of paucibacillary leprosy patients with a single skin lesion.
The recent World Health Organization multicentric field study on the treatment of paucibacillary (PB) leprosy patients with single skin lesion (SSL) and a single dose of rifampin-ofloxacin-minocycline (ROM) brought new hope to those who are engaged in the eradication of leprosy from India. Being encouraged by the WHO report, we undertook the present hospital-based study and found that PB leprosy patients with SSL were morphologically and histopathologically heterogeneous. The histological spectrum of SSL ranged from indeterminate through tuberculoid (TT) to borderline tuberculoid (BT) leprosy, and most patients had active BT leprosy. Ninety new, untreated PB leprosy patients with SSL were included in the present study for comparative assessment of the efficacies of ROM and ROM plus Convit vaccine therapies. Children, pregnant women, lactating mothers and patients with any thickening of nerves were excluded. All patients were bacteriologically negative (skin-smear test) but lepromin reactive. The patients were divided into two groups after proper matching for morphological and histological status of SSL: a) The test group included 60 patients and the control group included 30 patients. The test group was given a single dose of ROM initially and two injections of low-dose Convit vaccine, one initially and the other at the end of 3 months. b) The control group was given only a single dose of ROM initially. Both groups were followed clinically every 2 weeks for 6 months and retested for histological, bacteriological and lepromin status at the end of 6 months. Thereafter, they were followed clinically every month for another 6 months. In the test group, the SSL resolved in 33.3%, regressed in 48.3%, and remained active in 18.3% of the patients, while the granuloma disappeared in 70% of the cases. Only one patient developed neuritis, and in another patient the disease relapsed on the eighth month. On the other hand, the SSL in the control patients resolved, regressed and remained active in 13.3%, 63.3% and 23.3% of the cases, respectively, while the granuloma disappeared in 53.3% of the cases. In the seven patients who remained active, the disease course was progressive, and two of them developed neuritis. The clinical outcome of the patients treated with ROM plus low-dose Convit vaccine was statistically superior to those treated with single-dose ROM therapy alone.
Adjuvants, Immunologic↗
Measurement of surface alpha contamination using electret ion chambers.
Electret ion chambers are inexpensive, light-weight, commercially available, passive charge-integrating devices for accurate measurement of different radiations. Performance of electret ion chambers for surface alpha contamination measurement was evaluated. Ion chambers of two types and electrets of three thicknesses were used for the study. Calibration of the electret ion chambers was performed using reference alpha standards of different energies and radioactivities. Effects of various parameters such as chamber dimensions, electret thickness, alpha particle energy, position of alpha source from the chamber centerline, source localized or uniformly distributed, level of alpha contamination, Mylar window covering the chamber, and ambient radon and gamma radiation on the response of the electret ion chambers were determined. Suitable combinations of chambers and electrets to measure surface alpha contamination were determined.
Alpha Particles↗
Fungistatic and fungicidal activities of murine polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis.
Recently, a novel culture medium for detecting live yeast cells of Paracoccidioides brasiliensis was developed by Kurita et al. Using this culture medium, murine peritoneal polymorphonuclear leucocytes (PMN) were examined for fungistatic and fungicidal activities against P. brasiliensis yeast cells. The magnitude of the antifungal effect of PMN varied depending upon the fungal isolates used. PMN exhibited a killing effect on P. brasiliensis isolate Bt-4 in 2 h of coculture. In contrast, the other three fungal isolates employed were resistant to killing by PMN. However, PMN considerably suppressed the growth of isolates Tatu and Recife in a long-term assay (approximately 72 h). The growth of isolate Bt-9 was also suppressed by PMN during the first 24 h, but was found to be considerably promoted at 72 h of coculture. Interferon-gamma (IFN-gamma), but not tumour-necrosis factor-alpha, significantly augmented the antifungal activity of PMN. IFN-gamma-treated PMN exhibited a killing effect on isolates Tatu, Recife and Bt-9 after 24 h of coculture, and showed an enhanced killing effect on isolate Bt-4. Contact between PMN and fungal cells was required for PMN to exert the antifungal effect. Our results suggest that PMN, whether activated with cytokines or not, might play a critical role in host resistance in early infection with this fungus by buying time for development of more effective immunologic responses.
Animals↗
Influenza virus nucleoprotein interacts with influenza virus polymerase proteins.
Influenza virus nucleoprotein (NP) is a critical factor in the viral infectious cycle in switching influenza virus RNA synthesis from transcription mode to replication mode. In this study, we investigated the interaction of NP with the viral polymerase protein complex. Using coimmunoprecipitation with monospecific or monoclonal antibodies, we observed that NP interacted with the RNP-free polymerase protein complex in influenza virus-infected cells. In addition, coexpression of the components of the polymerase protein complex (PB1, PB2, or PA) with NP either together or pairwise revealed that NP interacts with PB1 and PB2 but not PA. Interaction of NP with PB1 and PB2 was confirmed by both coimmunoprecipitation and histidine tagging of the NP-PB1 and NP-PB2 complexes. Further, it was observed that NP-PB2 interaction was rather labile and sensitive to dissociation in 0.1% sodium dodecyl sulfate and that the stability of NP-PB2 interaction was regulated by the sequences present at the COOH terminus of NP. Analysis of NP deletion mutants revealed that at least three regions of NP interacted independently with PB2. A detailed analysis of the COOH terminus of NP by mutation of serine-to-alanine (SA) residues either individually or together demonstrated that SA mutations in this region did not affect the binding of NP to PB2. However, some SA mutations at the COOH terminus drastically affected the functional activity of NP in an in vivo transcription-replication assay, whereas others exhibited a temperature-sensitive phenotype and still others had no effect on the transcription and replication of the viral RNA. These results suggest that a direct interaction of NP with polymerase proteins may be involved in regulating the switch of viral RNA synthesis from transcription to replication.
Nucleocapsid Proteins↗
Influenza virus polymerase basic protein 1 interacts with influenza virus polymerase basic protein 2 at multiple sites.
Three polymerase proteins of influenza type A virus interact with each other to form the active polymerase complex. Polymerase basic protein 1 (PB1) can interact with PB2 in the presence or absence of polymerase acidic protein. In this study, we investigated the domains of PB1 involved in complex formation with PB2 in vivo, using coexpression and coimmunoprecipitation of the PB1-PB2 complex with monospecific antibodies. Results show that PB1 possesses at least two regions which can interact independently and form stable complexes with PB2. Both of these regions are located at the NH2 terminus of PB1; the COOH-terminal half of PB1 is not involved in interacting with PB2. Deletion analysis further demonstrated that the interacting regions of PB1 encompass amino acids (aa) 48 to 145 and aa 251 to 321. Linker insertions throughout the PB1 sequences did not affect complex formation with PB2. Deletion and linker-insertion mutants of PB1 were tested for polymerase activity in vivo. For this analysis, we developed a simplified assay for viral polymerase activity that uses a reporter chloramphenicol acetyltransferase gene containing the 5' and 3' ends of influenza viral promoter and nontranslating regions (minus sense) of the NS gene joined to a hepatitis delta virus ribozyme at its 3' end. This assay demonstrated that all deletion mutants of PB1 exhibited either background or greatly reduced polymerase activity irrespective of the ability to interact with PB2 and that all linker-insertion mutants except one at the extreme COOH end (L-746) of PB1 were also negative for viral polymerase activity. These results show that compared with complex formation of PB1 with PB2, the polymerase activity of PB1 was extremely sensitive to structural perturbation.
Binding Sites↗