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Biomedical subjects

A Chakrabarti

Publications and source records attributed to A Chakrabarti.

At least 19 recordsLinked to original sources
PubMed2007

Receptor-mediated internalization of chelator-PNA-peptide hybridization probes for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours.

Early external detection of cancer gene activity might enable early treatment of cancer and might reduce cancer mortality. We hypothesized that oncogene mRNA overexpressed at thousands of copies per malignant cell in a zone of transformed cells could be imaged externally by scintigraphic imaging, PET (positron emission tomography) or MRI (magnetic resonance imaging) with PNA (peptide nucleic acid) hybridization probes that include chelators for metal cations and a cyclized peptide analogue of IGF-1 (insulin-like growth factor 1), D(Cys-Ser-Lys-Cys), to mediate internalization by IGF1R (IGF-1 receptor) overexpressed on cancer cells. We observed that human MCF7 breast cancer cells that overexpress IGF1R efficiently internalized fluorescein-chelator-PNA-D(Cys-Ser-Lys-Cys) to the cytoplasm, but not with D(Cys-Ala-Ala-Cys). Scintigraphic imaging of MCF7 xenografts in immunocompromised mice revealed that CCND1 and MYC [(99m)Tc]chelator-PNA-D(Cys-Ser-Lys-Cys) probes yielded xenograft. PET imaging with [(64)Cu]chelator-PNA-D(Cys-Ser-Lys-Cys) yielded stronger signals. Scintigraphic imaging of human AsPC1 pancreas cancer xenografts with [(99m)Tc]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys) yielded strong xenograft signals. Stronger xenograft image intensities were obtained by PET imaging of [(64)Cu]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys). MRI required extension of chelator-polydiamidopropanoate dendrimers from the N-termini of the PNA probes to increase the number of contrast paramagnetic gadolinium (III) cations per probe. These results provide a basis for detection of oncogene activity in tissues from outside the body by hybridization with metal-chelator-PNA-peptides that are selectively internalized by cancer cells.

Animals↗
PubMed2006

Postoperative shoulder surgery initiative (POSSI): an interim report of major shoulder surgery as a day case procedure.

BACKGROUND: There are logistical and financial advantages to undertaking shoulder surgery in a day case setting. However, this approach is limited by postoperative pain being inadequately controlled by oral medication alone. We describe a pilot study investigating the feasibility and acceptance of community based continuous interscalene brachial plexus blockade (CIBPB) to provide effective analgesia for day case shoulder surgery. METHODS: Phase 1 consisted of five patients who received CIBPB for shoulder surgery. Following an overnight hospital stay they were assessed for discharge home with the interscalene catheter in situ. Once the safety and feasibility of the approach was documented, five more patients were recruited to Phase 2. These patients had the adequacy of analgesia assessed in the postoperative period and were discharged home on the same day as surgery. A district nurse visited twice daily and removed the catheter on the third day. Patient satisfaction was assessed using a discovery interview. RESULTS: Nine of the 10 patients experienced good analgesia. One patient was re-admitted because the catheter fell out. No patient experienced complications and the discovery interviews showed that the patients were satisfied with their management and pleased to be treated as a day case. CONCLUSIONS: POSSI proved that it was feasible to manage these patients in the community with support and training of the district nurses. Although extra community nursing hours are required, this technique has the potential for significant cost benefits with at least three bed days saved per patient.

Adult↗
PubMed2006

Computer simulation of diffusion-limited cluster-cluster aggregation with an Epstein drag force.

The motion of particles, dispersed in a medium, between collisions with each other can, in limiting situations, be either ballistic (straight line) or diffusive (random walker). The diffusive regime can be divided into two distinct subregimes. The "continuum regime" exhibits Stokes-Einstein-type diffusion (no-slip surface boundary condition) with a frictional coefficient proportional to the particle size (linear dimension). The "Epstein regime," as we shall refer to it, is characterized by a frictional coefficient proportional to the particle cross-sectional area, hence an Epstein-type diffusion (slip surface). The purpose of the current study is to illuminate the dynamics of dilute-limit aggregation in the Epstein regime. We present results from low volume fraction Monte Carlo simulations of cluster-cluster aggregation in the Epstein regime with the particle motion based on each particle's cross-sectional area. Our findings indicate that aggregates grown under Epstein conditions have a fractal dimension of approximately 1.8, similar to that of diffusion-limited cluster-cluster aggregates (DLCA) in the continuum regime. The kinetic exponent z in the Epstein regime is found to be z approximately 0.8, lower than its value for both the continuum regime DLCA (z = 1) and for the ballistic cluster aggregation regime (z approximately 2). Cluster size distribution data for Epstein systems are found to scale at large cluster sizes with exponents consistent with the kinetic data. A scaling argument for predicting the kinetic exponent and kernel homogeneity based on the mass or size dependence of the particle velocity and collision cross section is presented and is seen to give accurate results for dilute and intermediate values of particle volume fractions not only for the current study, but also for work done by other researchers with various choices for the aggregation kernel.

Journal Article↗
PubMed2006

Hybrid superaggregate morphology as a result of aggregation in a cluster-dense aerosol.

From the digitized pictures of soot clusters formed after the explosion of a hydrocarbon gas mixed with oxygen, the cluster morphology was determined by two different methods: structure factor and perimeter analysis. We find a hybrid, superaggregate morphology characterized by a fractal dimension of D approximately equal to 1.8 between the monomer size, ca. 50 nm, and 1 microm and D approximately equal to 2.6 at larger length scales up to approximately 10 microm. The superaggregate morphology is a consequence of late-stage aggregation in a cluster-dense regime near a gel point.

Journal Article↗
PubMed2006

Evidence for systemic oxidative stress in tobacco chewers.

OBJECTIVE: To evaluate erythrocyte malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione reductase (GR) in tobacco chewers, in view of possible oxidative stress in oral smokeless tobacco. MATERIAL AND METHODS: Sixty healthy male tobacco chewers, aged 30.6+/-4.7 years with a 3 to 10-year (7.37+/-2.1) history of tobacco chewing, were included in the study. Thirty-two healthy male volunteers, aged 26.5+/-4.8 years, served as controls. All the participants were from the same community and of similar dietary habits. RESULTS: The erythrocyte MDA level and activities of erythrocyte SOD and GR were estimated. There was a significant duration- (tobacco chewing) dependent increase in erythrocyte MDA levels along with a significant duration- (tobacco chewing) dependent decrease in erythrocyte SOD and GR activity. CONCLUSION: Oral smokeless tobacco causes a duration-dependent increase in oxidative stress.

Adult↗
PubMed2006

Microscopic, cultural and molecular evidence of disseminated invasive aspergillosis involving the lungs and the gastrointestinal tract.

A patient with acute promyelocytic leukaemia developed invasive aspergillosis post chemotherapy during a pancytopenic episode, clinically involving the lungs and the gastrointestinal tract. Dichotomously branched septate fungal hyphae were demonstrated microscopically in stools and sputa. Cultures of the samples yielded Aspergillus flavus, which were identical by RFLP and random amplification of polymorphic DNA analyses and antifungal MICs, proving disseminated disease. To the best of the author's knowledge, this is the first time that boluses of fungal hyphae have been demonstrated microscopically in the stools of a patient with gastrointestinal aspergillosis.

Adolescent↗
PubMed2006

An unusual case of mediastinal mass due to Fonsecaea pedrosoi.

Phaeohyphomycosis is a disease caused by dematiaceous fungi. Here, the first culture-proven case of mediastinal mass due to Fonsecaea pedrosoi is reported. The patient was a 40-yr-old male who had presented with history of dyspnoea and dysphagia. Computed tomography of the chest disclosed a mediastinal mass. Cultures of a specimen from the mediastinum grew Fonsecaea pedrosoi. The patient received amphotericin B and itraconazole and showed a remarkable recovery. Repeat computed tomography revealed a reduction in the mediastinal mass. The case highlights the need for a high degree of clinical suspicion and appropriate histopathological and mycological examination of clinical specimens.

Adult↗
PubMed2006

Polymerase chain reaction for early diagnosis of post-operative fungal endophthalmitis.

BACKGROUND AND OBJECTIVES: Fungal endophthalmitis is a devastating form of ocular infection and postoperative endophthalmitis following cataract surgery is the commonest form of such infection. Early diagnosis is very important for effective management of these patients. As conventional techniques take longer time and lacks sensitivity, polymerase chain reaction (PCR) for detection of fungal DNA was evaluated for early diagnosis of postoperative fungal endophthalmitis. METHODS: Fifty consecutive patients with postoperative endophthalmitis (excluding proven bacterial endophthalmitis) and 25 individuals undergoing pars plana vitrectomy (PPV) of non infectious aetiologies (control group) were included in the study. Aqueous/vitreous fluids, collected from these patients, were evaluated by conventional methods including direct microscopy and culture, and by PCR for detection of fungal DNA using panfungal primers (ITS1 and ITS4) for diagnosis of fungal aetiology. RESULTS: None of the controls were positive for fungal aetiology by microscopy, culture or PCR. Four patients were positive for fungal endophthalmitis by conventional method of diagnosis. PCR based method detected fungal DNA in three of these patients and in three additional patients who were negative on microscopy and culture. All six patients, who were positive for PCR, showed clinical improvement after full course of antifungal therapy. INTERPRETATION AND CONCLUSION: Compared to the conventional technique, PCR for detection of fungal DNA was found to be a rapid and more sensitive method in the early diagnosis of postoperative fungal endophthalmitis.

Adolescent↗
PubMed2005

Aggregation-fragmentation in a model of DNA-mediated colloidal assembly.

We present results from an off-lattice Monte Carlo simulation of DNA-mediated colloidal assembly. In this simulation, the aggregation-fragmentation of a binary mixture of DNA-coated colloidal particles is studied through a simplified model of base-pair hybridization. Bonding between monomers is modeled as a simple temperature-sensitive A/B-type interaction, where type A and B monomers can bond to only the opposite type (no A/A or B/B attachments are allowed). The actual chemistry of base-pair hybridization is not included in the model. The morphological structures of the clusters formed as well as the kinetics of growth are analyzed in our 2D simulations. The fractal dimension and kinetic growth exponents for clusters formed near the DNA "melting" temperature agree with those seen previously for 2D diffusion-limited cluster aggregation (DLCA) models. The clusters appear more compact, exhibiting signs of local order at intermediate temperature values. At higher temperatures, the formation of large clusters is not favorable under the action of temperature-dependent fragmentation, and the system eventually reaches a steady state as a collection of small aggregates. The temperature profile for this dissolution of the colloidal assembly is sharp, indicating that the selective hybridization process provides a highly sensitive measurement tool. At high temperatures, we analyze the steady-state behavior of the average cluster size in terms of an aggregation-fragmentation model.

Algorithms↗
PubMed2005

Synthesis of novel peptide nucleic acid-peptide chimera for non-invasive imaging of cancer.

A chelator-peptide-PNA-peptide chimera specific for KRAS has been prepared by continuous solid phase coupling with a C-terminal insulin-like growth factor 1 (IGF1) ligand, D(cys-ser-lys-cys), and N-terminal bis(S-benzoyl thioglycoloyl) diaminopropanoate chelator for radionuclide labeling. The probe was purified by RP-HPLC and characterized by MALDI-TOF mass spectroscopy. The probe was labeled with 99mTc and 64Cu. Both labeled probes accumulated in human pancreatic cancer xenografts in immunocompromised mice. Control experiments with mismatch chimeras and control xenografts will be necessary to determine the specificity of this molecular diagnostic strategy.

Animals↗
PubMed2005

Microbiology of systemic fungal infections.

The increased incidence of systemic fungal infections in the past two decades has been overwhelming. Earlier, it was pathogenic dimorphic fungi, which were known to cause systemic infections. However, starting from the 1960s, opportunistic fungi started causing more number of infections, especially in the immunocompromised host. More recently, newer and less common fungal agents are being increasingly associated with infection in immunosuppressed hosts. Amongst dimorphic fungi, infections due to Histoplasma capsulatum and Penicillium marneffei are increasingly reported in patients with AIDS in India. H. capsulatum is found country wide, but P marneffei remains restricted to Manipur state. Although both varieties of C. neoformans, C. neoformans var. neoformans (serotypes A & D), and C. neoformans var. gattii (serotypes B & C) are reported in India, most of the cases reported are of serotype A. Increased incidence of cryptococcosis is reported from all centers with the emergence of AIDS. Systemic infection due to species under Candida, Aspergillus and zygomycetes is widely prevalent in nosocomial setting, and outbreaks due to unusual fungi are reported occasionally from tertiary care centers. This global change in systemic fungal infections has emphasized the need to develop good diagnostic mycology laboratories in this country and to recognize this increasingly large group of potential fungal pathogens.

Humans↗
PubMed2004

Structure factor scaling in colloidal phase separation.

The dynamical scaling hypothesis for the structure factor, S (q) , in depletion-driven colloidal phase separation is studied by carrying out Brownian dynamics simulations. A true dynamical scaling is observed for shallow quenches into the two-phase coexistence region. In such a quench, compact clusters nucleate and grow with time and there is only one characteristic length scale in the system after an initial transient period. Scaling is satisfied beyond this initial period. In contrast, deep quenches lead to fractal cluster growth, and the system is controlled by two characteristic lengths that evolve differently in time [Huang, Oh, and Sorensen (HOS), Phys. Rev. E 57, 875 (1998)]. True dynamical scaling thus cannot be expected to hold. However, an apparent scaling for the structure factor is observed over some period of time when these two characteristic length scales become comparable to each other. We compare our simulation results for the total structure factor to theoretical predictions by HOS by writing it as a product of cluster-cluster and the averaged single-cluster structure factors, each with its own characteristic length.

Journal Article↗
PubMed2004

Cluster shape anisotropy in irreversibly aggregating particulate systems.

The results for cluster shape anisotropy over a broad range (10)(-3)-10(-1)) of monomer volume fractions, fv values, are presented for both two- (2d) and three-dimensional (3d) simulations of diffusion-limited (DLCA), ballistic-limited (BLCA), and reaction-limited (RLCA) cluster-cluster aggregation classes. We find that all three aggregation classes have different dilute-limit shape anisotropies, with the diffusion-limited model having the largest value of anisotropy and the reaction-limited model having the smallest. The simulation result for the cluster shape anisotropy for each of the three aggregation classes is slightly less than the corresponding prediction of the hierarchial model. In addition, we find excellent agreement between the 2d DLCA simulation results and experimental measurements of shape anisotropy. At late times, shape anisotropy decreases from the dilute-limit value.

Journal Article↗
PubMed2004

Kinetics of phase transformations in depletion-driven colloids.

We present results from a detailed numerical study of the kinetics of phase transformations in a model two-dimensional depletion-driven colloidal system. Transition from a single, dispersed phase to a two-phase coexistence of monomers and clusters is obtained as the depth of the interaction potential among the colloidal particles is changed. Increasing the well depth further, fractal clusters are observed in the simulation. These fractal clusters have a hybrid structure in the sense that they show hexagonal closed-packed crystalline ordering at short length scales and a ramified fractal nature at larger length scales. For sufficiently deep potential wells, the diffusion-limited cluster-cluster aggregation model is recovered in terms of the large-scale fractal dimension Df of the clusters, the kinetic exponent z, and the scaling form of the cluster size distribution. For shallower well depths inside the two-phase coexistence region, simulation results for the kinetics of cluster growth are compared with intermediate-stage phase separation in binary mixtures. In the single-phase region, growth kinetics agree well with a mean-field aggregation-fragmentation model of Sorensen, Zhang, and Taylor.

Journal Article↗
PubMed2004

Structural crossover in dense irreversibly aggregating particulate systems.

Cluster-cluster aggregation has been simulated by off-lattice Monte Carlo methods for diffusion-limited (DLCA), ballistic-limited, and reaction-limited cluster aggregation classes. We find that as the system evolves and becomes dense, the largest cluster develops a hybrid structure with mass fractal dimension D(f) approximately 2.6 over large length scales, while at smaller length scales, the early time dilute-limit fractal structure is frozen in. The largest cluster is thus an aggregate of smaller aggregates with a different fractal dimension, and we call it a "superaggregate." The crossover length separating the two morphologies, which we call the critical radius of gyration, can be calculated based on a simple theory that assumes a monodisperse cluster size distribution. This agrees well with simulation results for DLCA. However, for other classes we find that the increasing polydispersity in cluster size pushes the simulated crossover length radius of gyration to values systematically larger than the predicted value.

Journal Article↗
PubMed2004

Universal occurrence of soot superaggregates with a fractal dimension of 2.6 in heavily sooting laminar diffusion flames.

Using small-angle light scattering we show that a new phase of soot with size ca. 10 microm and a fractal dimension of D approximately equal to 2.6 exists in laminar diffusion flames for a wide range of heavily sooting fuels. This new phase appears to be a supramicrometer extension of the well-known submicrometer, D approximately equal to 1.8 phase of soot formed via diffusion-limited cluster aggregation (DLCA). The occurrence of this new soot phase correlates with an empirical sooting index for fuels. This supports a creation scenario in which these supramicrometer aggregates are created via a percolation of the submicrometer, D approximately equal to 1.8 aggregates.

Journal Article↗
PubMed2004

Molecular dynamics simulation of the transition from dispersed to solid phase.

Molecular dynamics simulations in two dimensions of particles interacting with finite potentials comparable to k(B)T yield aggregates which cross over from a fractal to a compact crystalline morphology. Growth kinetics and aggregate size distributions evolve from nonequilibrium to equilibrium limits.

Journal Article↗