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Biomedical subjects

S Rajagopal

Publications and source records attributed to S Rajagopal.

At least 37 records · Page 2Linked to original sources

Luminescence enhancement induced by aggregation of alkoxy-bridged rhenium(I) molecular rectangles.

Self-assembly of rhenium(I)-based molecular rectangles containing long alkyl chains has been achieved in one-pot synthesis by solvothermal methods. An enormous enhancement in the emission intensity, quantum yield, and lifetime of the rectangles has been observed when the solvent medium is changed from organic to aqueous. Addition of water favors the aggregation of Re(I) molecular rectangle resulting in the luminescence enhancement, and this phenomenon has been traced out using light scattering techniques.

Journal Article↗

Control of brackish water fouling mussel, Mytilopsis leucophaeata (Conrad), with sodium hypochlorite.

Though the Conrad's false mussel, Mytilopsis leucophaeata, is an important fouling animal in industrial cooling water systems, there are no published reports on the tolerance of this species to chlorination. A series of experiments was conducted to determine the effects of mussel size (2-20 mm shell length), season (breeding versus nonbreeding), nutritional status (fed versus starved) and acclimation temperature (5-30 degrees C) on the mortality pattern of M. leucophaeata under continuous chlorination (0.25-5 mg/L). The effect of mussel size on M. leucophaeata mortality in the presence of chlorine was significant, with 10 mm size group mussels showing greater resistance. At 0.25 mg/L residual chlorine, 2 mm size group mussels took 89 days to reach 100% mortality, whereas 10 mm size group mussels took 109 days. M. leucophaeata collected during nonbreeding season (December-April) was more tolerant to chlorine than those collected during breeding season (June-October). Nutritional status of the mussel had no significant influence on the chlorine tolerance of the mussel: fed and starved mussels succumbed to chlorine at equal rates. The effect of acclimation temperature on M. leucophaeata mortality in the presence of chlorine was significant. At 0.5 mg/L residual chlorine, mussels acclimated at 5 degrees C required 99 days to reach 95% mortality, whereas mussels acclimated at 30 degrees C required 47 days. A comparison of present data with previous reports suggests that resistance of M. leucophaeata to chlorination is higher than other mussel species causing fouling problems in The Netherlands ( Mytilus edulis and Dreissena polymorpha).

Animals↗

Changes in the structure of chlorophyll-protein complexes and excitation energy transfer during photoinhibitory treatment of isolated photosystem I submembrane particles.

The activity of light-induced oxygen consumption, absorption spectra, low temperature (77 K) chlorophyll fluorescence emission and excitation spectra were studied in suspensions of photosystem (PS) I submembrane particles illuminated by 2000 microE m(-2) s(-1) strong white light (WL) at 4 degrees C. A significant stimulation of oxygen uptake was observed during the first 1-4 h of photoinhibitory treatment, which rapidly decreased during further light exposure. Chlorophyll (Chl) content gradually declined during the exposure of isolated PSI particles to strong light. In addition to the Chl photobleaching, pronounced changes were found in Chl absorption and fluorescence spectra. The position of the major peak in the red part of the absorption spectrum shifted from 680 nm towards shorter wavelengths in the course of strong light exposure. A 6-nm blue shift of that peak was observed after 5-h illumination. Even more pronounced changes were found in the characteristics of Chl fluorescence. The magnitude of the dominating long-wavelength emission band at 736 nm located in untreated particles was five times reduced after 2-h exposure, whereas the loss in absolute Chl contents did not exceed 10% of its initial value. The major peak in low-temperature Chl fluorescence emission spectra shifted from 736 to 721 nm after 6-h WL treatment. Individual Chl-protein complexes differed in the response of their absorption spectra to strong WL. Unlike light-harvesting complexes (LHC), LHCI-680 and LHC-730, which did not exhibit changes in the major peak position, its maximum was shifted from 678 to 671 nm in CPIa complex after PSI submembrane particles were irradiated with strong light for 6 h. The results demonstrated that excitation energy transfer represents the stage of photosynthetic utilization of absorbed quanta which is most sensitive to strong light in isolated PSI particles.

Chlorophyll↗

Disruption of transforming growth factor beta-regulated laminin receptor function by expression of antisense laminin, a chain RNA in human colon cancer cells.

Transforming growth factor beta1 (TGFbeta) simultaneously induces the expression of fibronectin, fibronectin receptor, laminin, and laminin receptor (alpha6beta1 integrin) in the human colon cancer cell line Moser (Int J Cancer, 57:742, 1994). Induction of fibronectin and induction of fibronectin receptor by TGFB are tightly coupled, and disrupting fibronectin induction disrupts the induction of fibronectin receptor and cellular adhesion to fibronectin (J Cellular Physiol, 170:138, 1997). We recently demonstrated the efficacy of using antisense chain-specific laminin RNA expression vectors to disrupt the induction by TGFP of the multichain laminin molecule (J Cellular Physiol, 178:296, 1999). We now show in this report that Moser cells used alpha6 and beta1 integrins to adhere to laminin, and, as is the fibronectin and fibronectin receptor system, disrupting the induction by TGFbeta of the ligand laminin by the expression of antisense laminin A chain RNA disrupted the induction of 125I-laminin binding and cellular adhesion to laminin. Disrupting laminin induction also blocked the induction of alpha6 and beta1 integrin laminin receptor by TGFbeta. We conclude that disrupting the induction of the ligand laminin by TGFbeta disrupts TGFbeta-regulated laminin receptor function by suppressing the induction of alpha6 and beta1 integrins. Therefore, targeted disruption of the ligand laminin may be an effective means in disrupting the function of both the ligand and its receptor in cells that utilize the laminin and laminin receptor system in malignant cell behavior.

Colonic Neoplasms↗

Ectopic expression of eIF-4E in human colon cancer cells promotes the stimulation of adhesion molecules by transforming growth factorbeta.

Transforming growth factor beta1 (TGFbeta) inhibits cellular proliferation, promotes differentiation, and stimulates the expression and secretion of the extracellular matrix adhesion molecules fibronectin and laminin and the colon-associated intercellular adhesion molecule carcinoembryonic antigen. This is collectively called the TGFbeta-mediated adhesion response and occurs in the human colon cancer cell line Moser while the cell line KM12SM is relatively unresponsive to TGFbeta. We have previously shown that TGFbeta rapidly stimulates protein kinase C (PKC) phosphotransferase activity in the Moser cells and that the induction of the adhesion response (but not antiproliferation) by TGFbeta is dependent on PKC. Because resistance to growth factors may be due to translational suppression and the translation initiation factor eIF-4E may alleviate translational suppression, we determined the effect of eIF-4E expression on the responses of Moser and KM12SM cells to TGFbeta. Ectopic expression of eIF-4E in the TGFbeta-responsive Moser cells enhanced the activation of PKC by TGFbeta and the induction of the adhesion response, especially the secretion of adhesion molecules, but not the antiproliferative response. Ectopic expression of eIF-4E in the TGFbeta-resistant KM12SM cells increased TGFbeta stimulation of PKC and the TGFbeta-mediated adhesion response (but not antiproliferation). The secretion of adhesion molecules was significantly increased by TGFbeta. These results showed in these cells that eIF-4E promotes TGFbeta-regulated adhesion but not antiproliferation in a PKC-dependent manner.

Carcinoembryonic Antigen↗

Thermooptic effect in chloroplast thylakoid membranes. Thermal and light stability of pigment arrays with different levels of structural complexity.

In chloroplast thylakoid membranes, chiral macrodomains, i.e., large arrays of pigment molecules with long-range chiral order, have earlier been shown to undergo light-induced reversible and irreversible structural changes; such reorganizations did not affect the short-range, excitonic pigment-pigment interactions. These structural changes and similar changes in lamellar aggregates of the main chlorophyll a/b light-harvesting complexes exhibited a linear dependence on the intensity of light that was not utilized in photosynthesis. It has been hypothesized that the light-induced rearrangements are driven by a thermooptic effect, i.e., thermal fluctuations due to the dissipation of excess excitation energies [Barzda, V., et al. (1996) Biochemistry 35, 8981-8985]. To test this hypothesis, we have utilized circular dichroism (CD) spectroscopy to investigate the structural stability of the chiral macrodomains and the constituent bulk pigment-protein complexes of granal thylakoid membranes against heat and prolonged, intense illumination. (i) In intact thylakoid membranes, the chiral macrodomains displayed high stability below 40 degrees C, but they were gradually disassembled between 50 and 60 degrees C; the thermal stability of the chiral macrodomains could be decreased substantially by suspending the membranes in reaction media that were hypotonic or had low ionic strength. (ii) The chiral macrodomains were also susceptible to high light: prolonged illumination with intense white light (25 min, 2500 microE m(-)(2) s(-)(1), 25 degrees C) induced similar, irreversible disassembly to that observed at high temperatures; in different preparations, lower thermal stability was coupled to lower light stability. (iii) The light stability depended significantly on the temperature: between about 5 and 15 degrees C, the macrodomains in the intact thylakoids were virtually not susceptible to high light; in contrast, the same preillumination at 35-40 degrees C almost completely destroyed the chiral macrodomains. (iv) As testified by the excitonic CD bands, the molecular organization of the pigment-protein complexes in all samples exhibited very high thermal stability between about 15 and 65 degrees C, and virtually total immunity against intense illumination. These data are fully consistent with the hypothesis of a thermooptic effect, and are interpreted within the frame of a simple model.

Chlorophyll↗

Mechanism of selective oxidation of organic sulfides with Oxo(salen)chromium(V) complexes

The selective oxidation of organic sulfides to sulfoxides by oxo(salen)chromium(V) complexes in acetonitrile is overall second-order, first-order each in the oxidant and the substrate. The rate constant, k(2), values of several para-substituted phenyl methyl sulfides correlate linearly with Hammett sigma constants and the rho values are in the range of -1.3 to -2.7 with different substituted oxo(salen)chromium(V) complexes. The reactivity of different alkyl sulfides is in accordance with Taft's steric substituent constant, E(S). A mechanism involving direct oxygen atom transfer from the oxidant to the substrate rather than electron transfer is envisaged. Correlation analyses show the presence of an inverse relationship between reactivity and selectivity in the reaction of various sulfides with a given oxo(salen)chromium(V) complex and vice versa. Mathematical treatment of the results shows that this redox system falls under strong reactivity-selectivity principle (RSP).

Journal Article↗

Effect of ultraviolet-B radiation on intact cells of the cyanobacterium Spirulina platensis: characterization of the alterations in the thylakoid membranes.

Intact trichomes of Spirulina platensis are exposed to ultraviolet- B (UV-B) radiation (270-320 nm; 1.9 mW m(-2)) for 9 h. This UV-B exposure results in alterations in the pigment-protein complexes and in the fluorescence emission profile of the chlorophyll-protein complexes of the thylakoids as compared with thylakoids isolated from control dark-adapted Spirulina cells. The UV-B exposure causes a significant decrease in photosystem II activity, but no loss in photosystem I activity. Although there is no change in the photosystem I activity in thylakoids from UV-B-exposed cells, the chlorophyll a emission at room temperature and at 77 K indicates alterations associated with photosystem I. Additionally, the results clearly demonstrate that the photosystem II core antennae of chlorophyll proteins CP47 and CP43 are affected by UV-B exposure, as revealed by Western blot analysis. Furthermore, a prominent 94 kDa protein band appears in the sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) profile of UV-B-exposed cell thylakoids, which is absent from the control thylakoids. This 94 kDa protein appears not to be newly induced by UV-B exposure, but could possibly have originated from the UV-B-induced cross-linking of the thylakoid proteins. The exposure of isolated Spirulina thylakoids to the same intensity of UV-B radiation for 1-3 h induces losses in the CP47 and CP43 levels, but does not induce the appearance of the 94 kDa protein band in SDS-PAGE. These results clearly demonstrate that prolonged exposure of Spirulina cells to moderate levels of UV-B affects the chlorophyll a-protein complexes and alters the fluorescence emission spectral profile of the pigment-protein complexes of the thylakoid membranes. Thus, it is clear that chlorophyll a antennae of Spirulina platensis are significantly altered by UV-B radiation.

Chlorophyll↗

Assessment of the levels of chlorinated pesticides in breast milk in Kuwait.

Breast milk samples, randomly collected from 32 Kuwaiti donors were analysed for chlorinated pesticides. DDE residues ranged from 127 to 3333 micrograms/kg, averaging, 833 micrograms/kg, expressed on a fat weight basis. DDT levels ranged from 0.6 to 67 micrograms/kg fat and averaged 12.4 micrograms/kg, fat. High DDE/DDT ratios were found, which indicated that the exposure to DDT, in most cases, happened quite some time ago. In addition many of the samples also contained isomers of HCH, heptachlor-epoxide, aldrin, dieldrin and endrin. Residue levels of non-DDT pesticides were generally low. Overall levels of DDT-pesticides in Kuwaiti milk samples were lower than levels reported from other Middle Eastern countries, although methodologies may not be directly comparable.

Environmental Exposure↗

Differentiation-promoting effect of 1-O (2 methoxy) hexadecyl glycerol in human colon cancer cells.

Alkylglycerols are naturally occurring bioactive ether lipids found in great abundance in the livers of many marine species. In this study, we evaluated the differentiation-promoting potential of a methoxy substituted alkylglycerol--1-O (2 methoxy) hexadecyl glycerol (MHG)--to promote a more benign or differentiated phenotype in human colon cancer cells. Three cell lines with different biological and phenotypic properties were used. They were the moderately differentiated and growth factor-responsive Moser, the growth factor-unresponsive and malignant HT29, and the poorly differentiated and growth factor-unresponsive HCT116. Treatment of these cell lines with MHG resulted in a downmodulation of cellular proliferation, a reduced propensity for anchorage-independent growth, and a reduced capacity in cellular invasion. Induction of the colon-associated and differentiation-related molecule carcinoembryonic antigen was also observed in the three cell lines. Induction of the transformation-sensitive and differentiation-related glycoprotein fibronectin was observed in the HT29 cells. It is concluded that MHG was biologically active and promoted a more benign or differentiated phenotype in these colon cancer cells. Since differentiation-inducing agents may possess chemoprevention properties, the use of MHG and the alkylglycerols in inducing differentiation or in chemoprevention of malignant diseases warrants further investigation.

Antineoplastic Agents↗

Efficacy and specificity of antisense laminin chain-specific expression vectors in blocking laminin induction by TGFbeta1: effect of laminin blockade on TGFbeta1-mediated cellular responses.

Transforming growth factorbeta1 (TGFbeta1) elicits a multitude of cellular responses from the epithelial-derived human colon cancer Moser cells. TGFbeta1 induces the expression of laminin and fibronectin, and previous studies show that the induction of fibronectin is functionally associated with the regulation of carcinoembryonic antigen (CEA) expression by TGFbeta1 (Huang and Chakrabarty, 1994, J Biol Chem 269:28764-28768). In this study we constructed antisense laminin chain-specific expression vectors and determined their efficacy in blocking the expression and the induction of the large multichain laminin molecule by TGFbeta1. We also determined the functional role of laminin in several TGFbeta1-mediated responses: growth inhibition, downmodulation of anchorage-independent growth, and cellular invasion. Expression of either antisense laminin chain A, B1, or B2 RNA resulted in a downmodulation of endogenous laminin mRNA expression and blocked the induction of laminin protein by TGFbeta1 without affecting the induction of other adhesion molecules such as fibronectin or CEA. It is concluded that antisense RNA directed to only one of the laminin chains was sufficient to disrupt the induction of the complex laminin molecule in quite a specific manner. Expression of antisense laminin RNA downregulated cellular adhesion to extracellular matrix (ECM) laminin and blocked the ability of TGFbeta1 to upmodulate adhesion to ECM laminin. Expression of antisense laminin RNA, however, did not alter the downregulating effect of TGFbeta1 on cellular proliferation, anchorage-independent growth, or cellular invasion, suggesting that the induction of laminin did not play a significant functional role in these TGFbeta1-mediated cellular responses. It is likely that other adhesion pathways may be involved in mediating the action of TGFbeta1 in this cell line.

Carcinoembryonic Antigen↗

Percutaneous transvenous mitral commissurotomy for significant calcific mitral stenosis: utility of the stepwise balloon dilatation technique and follow-up results.

The present study examined the utility of the stepwise balloon dilatation technique in 41 patients with significant calcific mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Thirty-five patients (85.4%) had a successful procedure; one patient developed cardiac tamponade and underwent mitral valve replacement. The mitral valve area increased from 0.9 +/- 0.2 cm2 to 1.7 +/- 0.3 cm2 following PTMC. Increase in mitral regurgitation (MR) was seen in 11 patients (26.8%). All patients showed improvement in functional class of > or =1 level following PTMC, which was sustained in 34 patients at follow-up. At a mean follow-up period of 20 +/- 12 months (range 3-51 months) in 35 patients, 26 patients (74.3%) were in New York Heart Association (NYHA) functional Class I, 8 patients (22.9%) were in NYHA Class II, and 1 patient (2.8%) was in NYHA Class III. The cumulative 4-year cardiac event-free survival rate was 81.8%. However, patients with grade 4+ calcification had only 50% event-free survival rate. At follow-up, an increased incidence of cardiac events was seen in female patients as compared with male patients (83.3% versus 16.7%). Restenosis was seen in 3 patients (8.6%). One patient underwent repeat PTMC 37 months after the initial procedure. There was no incidence of death or mitral valve replacement at follow-up. We conclude that the stepwise balloon dilatation technique can be safely and effectively applied for patients with significant calcific mitral stenosis to achieve an optimal mitral valve area with low incidence of significant increase in MR. Favorable long-term benefits also accrue in the form of improved functional status and low incidence of repeat procedures (repeat PTMC or mitral valve replacement). The majority of patients (74.3%) were in NYHA functional class I without medication. Patients with grade 4+ calcification show less benefit from PTMC and may be considered for mitral valve replacement. Cardiac events occur more frequently in female patients than in male patients during follow-up.

Adult↗

Differentiation-inducing effect of retinoic acid, difluoromethylornithine, sodium butyrate and sodium suramin in human colon cancer cells.

We investigated the relative effectiveness of four differentiation-inducing chemicals to induce a more normal or benign phenotype in the human colon cancer cell lines Moser and HT29. The differentiation-inducing capability of all-trans retinoic acid (ATRA), difluoromethylornithine (DFMO), sodium butyrate (NaB) and sodium suramin (NaS) was evaluated in terms of the efficacy of these chemicals in inhibiting cellular proliferation, growth in soft agarose, invasion of matrigel and induction of morphological alteration. The relative ability of these chemicals to induce production of the differentiation-related molecules fibronectin and carcinoembryonic antigen was also determined. Overall, ATRA was found to be the most effective chemical in inducing differentiation as measured by these parameters. The Moser cells were more susceptible to differentiation induction by comparison with the HT29 cells. Both similarities and differences in the cellular responses to DFMO, NaB and NaS were also observed for the Moser and HT29 cells. The differences in cellular responses to these chemicals may be due to different phenotypic properties of these two cell lines and different mechanisms of action of these chemicals.

Antineoplastic Agents↗

Ultraviolet-B effects on Spirulina platensis cells: modification of chromophore-protein interaction and energy transfer characteristics of phycobilisomes.

Exposure of ultraviolet-B (280-320 nm, 1.9 mW m-2 s-1) radiation of intact Spirulina platensis for 9 h caused specific loss of the 85.5 KDa anchor protein of phycobilisomes, the major light-harvesting antenna complex of photosystem II. Associated with the loss of 85.5 KDa protein, the UV-B irradiation also caused photobleaching of phycobilins and alteration in the chromophore protein interactions, as evidenced from the visible circular dichroic measurements, and it also affected the energy transfer process within the phycobilisomes, as inferred from the low-temperature, 77 K, fluorescence spectral analysis. Our results, thus, clearly demonstrate for the first time that the phycobilisomes effectively act as targets for UV-B induced damage of photosynthetic apparatus in cyanobacteria.

Bacterial Proteins↗

Modulation of cellular proliferation and production of prostate-specific antigen and matrix adhesion molecules in human prostate carcinoma cells by polypeptide growth factors: comparative analyses of MDA PCa2a with established cell lines.

The cellular responses of a newly established and early-passage human prostate adenocarcinoma cell line, MDA PCa2a, to transforming growth factor (TGF) beta1, epidermal growth factor (EGF), and TGFalpha were characterized in terms of proliferation, production of prostate-specific antigen (PSA), fibronectin (FN) and laminin (LM). The responses of the MDA PCa2a cells were compared with those of the well-established human prostate carcinoma cell lines LNCap, PC3, and DU145. The MDA PCa2a cells were more responsive to the growth-inhibitory effect of TGFbeta1 than the established cell lines. The androgen-responsive cell lines (MDA PCa2a and LNCap) were relatively responsive to the growth-stimulatory effect of EGF and TGFalpha whereas the androgen-independent lines (PC3 and DU145) were not. Only the androgen-responsive cells produced PSA, which was further upregulated by treatment with growth factors. The androgen-independent cells did not produce PSA, and growth factors had no effect on PSA production. However, all cell lines produced abundant amounts of FN and LM, and the levels of production of these molecules were subject to modulation by growth factors. It is concluded that each growth factor elicits diverse and distinct responses in prostate carcinoma cells, which may reflect the involvement of diverse post-receptor signal pathways.

Adenocarcinoma↗

Percutaneous Transvenous Mitral Commissurotomy for Post-Surgical Mitral Restenosis: Acute Outcome and Analysis of Factors Influencing Results.

The present study examined the utility of percutaneous transvenous mitral commissurotomy (PTMC) for post-surgical mitral restenosis (Group I, n = 71 patients), and the factors influencing the outcome of the procedure. The results of PTMC were also compared with a group of patients (Group II, n = 70 patients), who underwent PTMC for de novo mitral stenosis. Both the groups were matched for age, pre-procedure mitral valve area and echocardiographic score. PTMC was successful in 60 patients (85%) in group I and in 68 patients (97%) in group II (p < 0.05). However, the final mitral valve area achieved was similar between the two groups (1.8 +/- 0.3 vs. 1.9 +/- 0.2 sq.cm, p = NS). Patients in group I had significantly greater mitral valve calcification (0.6 +/- 0.8 vs. 0.3 +/- 0.6, p < 0.05). Multiple regression analysis of results in patients with post-surgical restenosis revealed that only basal mean pulmonary artery pressure and basal cardiac index correlated significantly with increase in valve area. Mitral valve leaflet mobility, thickness and subvalvular deformity did not correlate significantly with the increase in mitral valve area. CONCLUSION: PTMC is a safe procedure for post-surgical mitral restenosis with negligible complication, with a higher success and significantly lower complication rate than that reported for repeat surgical commissurotomy. Although patients with surgical restenosis had a greater degree of calcification of mitral valve leaflets; only basal mean pulmonary artery pressure and cardiac index significantly influenced the increase in mitral valve area. Increased fibrosis of mitral leaflet following surgery probably adversely influences the results of PTMC for post-surgical mitral restenosis.

Journal Article↗