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Biomedical subjects

S Ghose

Publications and source records attributed to S Ghose.

At least 19 recordsLinked to original sources

Comparison of linear gradient and displacement separations in ion-exchange systems.

The linear gradient mode of chromatography is the most widely employed mode of operation in ion-exchange chromatographic separations. However, in recent years, the displacement mode has received considerable attention because of its promise of high throughput and high resolution. To enable a comparison of these two modes of chromatography, it is essential to identify the optimum operating conditions for each. We employed an iterative algorithm to carry out the necessary optimization. The Steric Mass Action model of ion-exchange chromatography is used in concert with the solid-film linear-driving force model to describe the chromatographic behavior of the solutes in these systems. The performances of displacement and gradient modes of chromatography are compared for different types of separation problems. It turns out that for "easy" separations, both the modes are equally effective. However, for challenging separations, the displacement mode is superior to the gradient mode. Our results shed significant light on the performance of gradient and displacement modes in protein ion-exchange systems.

Adsorption↗

Necrotizing periorbital Fusarium infection--an emerging pathogen in immunocompetent individuals.

Fungal infections of the skin and deeper tissues of the periorbital region are quite rare. We report a case of a localized, deep periorbital necrotizing Fusarium infection in an otherwise healthy, elderly lady. Since the clinical features and histopathological findings of Fusarium infection are by no means characteristic, the definitive diagnosis was achieved with the help of microbiological examination of cultured organisms. A combined medical and surgical therapy led to adequate control of infection. To conclude, localized, deep periorbital necrotizing soft tissue infection by Fusarium in an immunocompetent lady is not reported in literature. One should have a high index of suspicion for emerging fungal pathogens in the differential diagnosis of necrotizing orbital or adnexal conditions, even in an immunocompetent patient. The histologic findings of septate, branching hyphae and vascular invasion cannot distinguish Fusarium species from various other moulds such as Aspergillus species; microbiologic studies are essential for confirming the diagnosis.

Amphotericin B↗

Atomic motion in magneto-optical double-well potentials: a testing ground for quantum chaos.

We have identified ultracold atoms in magneto-optical double-well potentials as a very clean setting in which to study the quantum and classical dynamics of a nonlinear system with multiple degrees of freedom. In this system, entanglement at the quantum level and chaos at the classical level arise from nonseparable couplings between the atomic spin and its center of mass motion. The main features of the chaotic dynamics are analyzed using action-angle variables and Poincaré surfaces of section. We show that for the initial state prepared in current experiments [D. J. Haycock et al., Phys. Rev. Lett. 85, 3365 (2000)], classical and quantum expectation values diverge after a finite time, and the observed experimental dynamics is consistent with quantum-mechanical predictions. Furthermore, the motion corresponds to tunneling through a dynamical potential barrier. The coupling between the spin and the motional subsystems, which are very different in nature from one another, leads to interesting questions regarding the transition from regular quantum dynamics to chaotic classical motion.

Journal Article↗

Characterization and modeling of monolithic stationary phases: application to preparative chromatography.

A methodology for characterizing and modeling preparative separations on monolithic ion-exchange stationary phases is presented. A dimensionless group analysis was carried out to determine the relative importance of mass transfer and kinetic resistances on this stationary phase. In contrast to conventional beaded morphologies, the continuous bed stationary phase was found to possess enhanced mass transport properties resulting in kinetic resistance as the dominant non-ideality. Accordingly, a reaction-dispersive steric-mass action formalism was successfully utilized for simulating preparative displacement chromatography on this resin. Since kinetics were found to be important on this column morphology, mobile phase salt concentration was found to be an important variable during displacement chromatography on this stationary phase. An increase in the mobile phase salt concentration was found to significantly improve the displacement separation of a model protein mixture. The formalism presented in this paper provides a better understanding of preparative chromatography in monolithic resin systems and a means of simulating separations on this class of chromatographic stationary phases.

Adsorption↗

Attenuation coefficients of soils and some building materials of Bangladesh in the energy range 276-1332 keV.

The linear and mass attenuation coefficients of different types of soil, sand, building materials and heavy beach mineral samples from the Chittagong and Cox's Bazar area of Bangladesh were measured using a high-resolution HPGe detector and the gamma-ray energies 276.1, 302.8, 356.0, 383.8, 661.6 and 1173.2 and 1332.5 keV emitted from point sources of 133Ba, 137Cs and 60Co, respectively. The linear attenuation coefficients show a linear relationship with the corresponding densities of the samples studied. The variations of the mass attenuation coefficient with gamma-ray energy were exponential in nature. The measured mass attenuation coefficient values were compared with measurements made in other countries for similar kinds of materials. The values are in good agreement with each other in most cases.

Bangladesh↗

Management of retinoblastoma with radiation.

OBJECTIVE: To evaluate the role of radiation therapy in the management of retinoblastoma. DESIGN: Retrospective analysis. METHOD: From January 1993 to March 1994, one hundred and eleven children (150 eyes) of retinoblastoma were referred for radiotherapy. The diagnosis was based on clinical examination and ocular ultrasonogram for both the eyes. The radiation treatment policy involved 40 Gy in 20 fractions over 4 weeks delivered with sedation for children under 1 year of age, 36 Gy in 9 fractions over 3 weeks under ketamine anesthesia for 1-4 years of age and for >4 years of age, a dose of 50 Gy in 25 fractions over 5 weeks. The initial tumor regression was evaluated by A and B mode ultrasonography and/or CT scan. RESULTS: The age distribution ranged from two months to six years (median - 20 months). Bilaterality was observed in 39 out of 111 cases (35%). The male to female ratio was 1.8:1. Eighty two of the 111 children were treated by definitive external beam radiation to one or both eyes. Fifteen cases received adjuvant radiotherapy after enucleation, and 14 had extensive disease for which palliative radiotherapy was offered. We observed a complete response in 54% of cases, partial response in 32%, and none in 14% of cases. Forty per cent (40%) eye survival was documented at the end of 28 months. The complication rate encountered was about 15%. CONCLUSION: Radiotherapy is an effective modality of treatment in significant number of patients with retinoblastoma. However, it requires appropriate fractionation, precise colimation and careful immobilization with general anesthesia.

Child↗

Evaluation of potentiating effect of a drop of lignocaine on tropicamide-induced mydriasis.

PURPOSE: To analyze whether preinstillation of lignocaine potentiates mydriasis by tropicamide in dark eyes and to determine possible mechanisms for this effect. METHODS: This investigation was conducted in two phases, the first being a double-masked, placebo-controlled, randomized clinical trial, enrolling 60 healthy dark brown eyes in 30 subjects aged 7 to 58 years. The control eye received a drop of (nonlignocaine) placebo before tropicamide 1%, and the contralateral study eye received a 4% lignocaine drop 3-minutes before the 1 drop of tropicamide was administered. A ruled pupillometer recorded pupil diameters every 10 minutes for 50 minutes. In phase II, to elucidate pathomechanisms after lignocaine, corneal and tear parameters were compared with baseline records in a further 60 such eyes. RESULTS: Pupillary diameters in the study eyes increased by 3.62 +/- 0.75 mm, significantly more than in the placebo (control) group (P = 0.000). Ninety percent of study eyes attained the clinically significant 6-mm size with preinstillation of lignocaine-many more than the 67% of control eyes (P = 0.016). The median time to achieve this critical 6-mm size was significantly faster in the study group (P = 0.005). In phase II, the 1 drop 4% lignocaine did not show corneal changes with slit lamp or fluorescein staining and did not reduce media clarity or induce a significant change in tear pH. It markedly decreased Schirmer values (P = 0.000), reduced tear break-up time (P = 0.003), and increased corneal thickness measured by optical pachymetry (P = 0.010). CONCLUSIONS: The phase II findings indicate corneal microepithelial damage and reduced tearing. Both may enhance intraocular penetration and hence potentiation of tropicamide. This remarkable phenomenon could find use with many other important topical medications.

Adolescent↗

Expanded bed chromatography of proteins in small-diameter columns. II. Methods development and scale up.

The scaled down system developed in Part I of this series was further validated by using a 1-cm diameter column for method development studies for the separation of two model proteins, alcohol dehydrogenase and alpha-glucosidase, from unclarified yeast homogenate by hydrophobic interaction expanded bed chromatography based on the STREAMLINE matrix. The efficacy of solids removal and establishment of optimal binding and separation condition by stepwise elution were investigated. Equilibration of the EBA column and loading at high salt strengths affected the subsequent recovery of the two target proteins. Although good resolution between the target proteins could be achieved, peak tailing was found to be a consistent problem. The optimised separation protocol was scaled up 25-fold to a column diameter of 5.0 cm. The results were in good agreement with the run conducted in the 1-cm column, indicating the potential of using the small columns as an viable approach for method scouting and development studies.

Adsorption↗

Expanded bed chromatography of proteins in small diameter columns. I. Scale down and validation.

The use of large columns for expanded-bed chromatography in protein adsorption and purification can pose limitations in method scouting due to the high volumes of consumables involved in optimisation runs. Scaling down this technique would provide a practical and necessary first step for demonstrating its feasibility in very small beds. The performance of three columns of diameters 5.0, 1.0 and 0.5 cm were compared in terms of the bed expansion, hydrodynamics and breakthrough for lysozyme adsorption onto STREAMLINE-SP. This represented a scale-down factor of a 100-fold from the 5-cm column and the success was judged by the insignificant changes in performance based on the selected criteria. Bed characterisation and breakthrough runs indicated good plug flow behaviour, despite the high particle size to column diameter ratio in the smaller columns. The column efficiency was found to be sensitive to the vertical alignment, making it an important issue in scale down. The results of these investigations show that small diameter columns can be effectively used for mimicking the behaviour in scale up systems providing a useful tool for method scouting studies.

Adsorption↗

Parental age in Indian patients with sporadic hereditary retinoblastoma.

There is a consistent correlation between sporadic hereditary retinoblastoma and parental age. It has been proven beyond doubt that the birth rank is correlated with parental age. In the present study, a test for the effect of birth rank was performed in order to assess the risk of developing retinoblastoma with increased parental age. The study of the effect of birth rank showed a significant association between sporadic retinoblastoma (bilateral and unilateral) and late para, indicating that fresh germline mutations must have taken place in some of the sporadic cases. An investigation of the effect of birth rank on familial cases, obtained from published papers and our own series, showed that familial retinoblastoma is significantly associated with early para, suggesting early parental age. Further analysis of the mean paternal and maternal ages of sporadic cases (bilateral and unilateral) showed that the mean paternal age of sporadic bilateral (sporadic hereditary) cases was higher than that of sporadic unilateral cases (p<0.05). No such correlation was seen with mean maternal age. Thus, the present study shows that a high paternal age may be associated with sporadic bilateral (sporadic hereditary) retinoblastoma.

Adult↗

Induction of erythroid differentiation by altered Galpha16 activity as detected by a reporter gene assay in MB-02 cells.

Heterotrimeric G proteins may assume modulatory roles in cellular proliferation and differentiation. The G protein alpha-subunit Galpha16, which is specifically expressed in hematopoietic cells, is highly regulated during differentiation of normal and leukemic cells. In human erythroleukemia cells, suppression of Galpha16 inhibited cellular growth rates. A reporter gene system was established to assess the role of Galpha16 on erythroid differentiation of MB-02 erythroleukemia cells. It is based on transient transfection with a plasmid that expresses green fluorescent protein under the control of the beta-globin promoter. Expression of Galpha16 led to a significant increase in green fluorescent protein-positive cells, as did transfection with a Galpha16 antisense plasmid (154 and 156% of controls, respectively). The GTPase-deficient, constitutively active mutant of Galpha16, Galpha16R186C, further stimulated differentiation to 195% of control values. Because the effect of Galpha16 is triggered most efficiently by the GTP-bound protein, an indirect action through interference of overexpressed Galpha16 with G protein betagamma-subunits can be excluded. The corresponding mutant of Galphaq (GalphaqR182C), the phylogenetically closest family member of Galpha16, had no effect. The data define a specific role for Galpha16-dependent signal transduction in cellular differentiation: deviations from optimal levels of Galpha16 functional activity lead to reduced growth rates and promote differentiation in hematopoietic cells.

Animals↗

Diagnostic intraocular fine-needle aspiration biopsy--An experience in three cases of retinoblastoma.

Ophthalmoscopically guided intraocular fine-needle aspiration biopsy (FNAB) under general anesthesia was performed in three suspected cases of retinoblastoma (Rb). The first case presented with uveitis and the second with unusual radiological features. The third case had classical clinical features of bilateral Rb but the parents refused enucleation. After a cytologic diagnosis of retinoblastoma, two cases were subjected to enucleation and a histologic confirmation was obtained. The present article discusses the technique of guided intraocular FNAB and its limitations as well as utility in the preoperative diagnosis of retinoblastoma (Rb). The authors are of the opinion that FNAB should be considered a viable diagnostic option in selected cases of leucocoria when conventional investigative modalities prove inconclusive or for tissue diagnosis when a patient of suspected Rb refuses enucleation.

Biopsy, Needle↗

Mobilization of intracellular calcium stores participates in the rise of [Ca2+]i and the toxic actions of the HIV coat protein GP120.

The HIV envelope glycoprotein, GP120, increases intracellular Ca2+ concentration and induces degeneration of human and animal neurons in culture. Using patch-clamp recordings and Ca2+ imaging techniques, we have now examined the contribution of intracellular stores of calcium in the effects of GP120. We report that in rat hippocampal neuronal cultures, GP120 induces a dramatic and persistent increase in [Ca2+]i which is prevented by drugs that either deplete (caffeine, carbachol, thapsigargin) or block (dantrolene) Ca2+ release from intracellular stores. In contrast, N-methyl-d-aspartate (NMDA) receptors or voltage-dependent calcium channels do not participate in these effects, as: (i) the increase in [Ca2+]i was not affected by NMDA receptor antagonists or calcium channel blockers; and (ii) and GP120 did not generate any current in whole-cell recording. Dantrolene, a ryanodine stores inhibitor, also prevented neuronal death induced by GP120. Our results show that the GP120-induced rise in [Ca2+]i originates from intracellular calcium stores, and suggest that intracellular stores of calcium may play a determinant role in the pathological actions of GP120.

Animals↗

Ocular extramedullary myeloid cell tumour in children: an Indian study.

Thirty-two children with extramedullary myeloid cell tumour (EMT) who constituted 41 per cent of children with acute myeloid leukaemia (AML) were studied to ascertain their laboratory characteristics and potential problems in diagnosis. The diagnosis, established by peripheral blood smear and/or bone marrow examination, was AML (n = 29) and refractory anaemia with excess blasts in transformation (RAEB-t; n = 3). The six referred patients in whom the diagnosis had been missed, and two cases wrongly reported as histiocytosis on aspiration cytology, were those in whom a peripheral blood smear had not been examined. It is concluded that diagnostic work-up of proptosis must include a full haemogram, meticulous peripheral blood smear examination, repeated if necessary, and bone marrow examination where relevant. RAEB-t cases with extramedullary myeloid cell tumour should be classified as acute myeloid leukaemia.

Acute Disease↗

The effect of column verticality on separation efficiency in expanded bed adsorption.

The effect of column verticality on liquid dispersion and separation efficiency in expanded bed adsorption columns was investigated using 1 and 5 cm diameter columns. Column misalignment of only 0.15 degree resulted in the reduction of the Bodenstein number from 140 to 50 for the 1 cm dia. column and from 75 to 45 for the 5 cm dia. column. This degree of misalignment was not detectable by visual assessment of adsorbent particle movement within the column. Depending on the relative importance of transport limitations, kinetic limitations and dispersion to any specific separation, this increase in dispersion with column alignment can significantly affect separation efficiency. Pure protein breakthrough profiles resulting from the application of bovine serum albumin onto STREAMLINE Q XL demonstrated that, at 10% breakthrough, 7.8% more protein could be applied to a vertical 1 cm dia. column compared to the same column misaligned by 0.15 degree. When an unclarified yeast homogenate was applied to a 1 cm dia. vertical column packed with STREAMLINE DEAE, 10% breakthrough of glucose-6-phosphate dehydrogenase (G6PDH) corresponded to a load 55% greater compared to the same column aligned 0.185 degree off-vertical. The G6PDH breakthrough curves for vertical and 0.15 degree off-vertical runs performed using a 5 cm column were essentially indistinguishable.

Adsorption↗

Absence of pericentromeric heterochromatin (9qh-) in a patient with bilateral retinoblastoma.

The polymorphisms of constitutive heterochromatin regions, present on chromosomes 1, 9, 16 and Y, are inherited in a Mendelian fashion. The C-band heteromorphism has been reported to be associated with various types of cancer. Heterochromatin is considered to play a role in protecting genome against the mutagens. Changes in the quantity and proportion of the different types of satellite DNA might increase the genetic susceptibility in people with heterochromatic variations, which in turn cause chromosome instability and predispose the individual to cancer. We report a case of bilateral retinoblastoma with complete absence of pericentromeric heterochromatin on one of the chromosomes number 9. A similar deficiency of pericentromeric heterochromatin on chromosome number 9 and 16 has been reported in a phenotypically normal individual and a Down syndrome case, respectively. This deficiency was found to be inherited from the father in all the three cases. Complete absence of pericentromeric heterochromatin of chromosome 9 is not being reported in association with cancer syndromes. Further studies are necessary to understand the role of this factor in normals and in those with cancer susceptibility, specially with retinoblastoma and the paternal origin of this deficiency.

Chromosome Deletion↗

N-acetylaspartylglutamate stimulates metabotropic glutamate receptor 3 to regulate expression of the GABA(A) alpha6 subunit in cerebellar granule cells.

We have shown that the vertebrate neuropeptide N-acetylaspartylglutamate (NAAG) meets the criteria for a neurotransmitter, including function as a selective metabotropic glutamate receptor (mGluR) 3 agonist. Short-term treatment of cerebellar granule cells with NAAG (30 microM) results in the transient increase in content of GABA(A) alpha6 subunit mRNA. Using quantitative PCR, this increase was determined to be up to 170% of control values. Similar effects are seen following treatment with trans-1-aminocyclopentane-1,3-dicarboxylate and glutamate and are blocked by the mGluR antagonists (2S,3S,4S)-2-methyl-2-(carboxycyclopropyl) glycine and (2S)-alpha-ethylglutamic acid. The effect is pertussis toxin-sensitive. The increase in alpha6 subunit mRNA level can be simulated by activation of other receptors negatively linked to adenylate cyclase activity, such as adenosine A1, alpha2-adrenergic, muscarinic, and GABA(B) receptors. Forskolin stimulation of cyclic AMP (cAMP) levels abolished the effect of NAAG. The change in alpha6 levels induced by 30 microM NAAG can be inhibited in a dose-dependent manner by simultaneous application of increasing doses of the beta-adrenergic receptor agonist isoproterenol. The increase in alpha6 mRNA content is followed by a fourfold increase in alpha6 protein level 6 h posttreatment. Under voltage-clamped conditions, NAAG-treated granule cells demonstrate an increase in the furosemide-induced inhibition of GABA-gated currents in a concentration-dependent manner, indicating an increase in functional alpha6-containing GABA(A) receptors. These data support the hypothesis that NAAG, acting through mGluR3, regulates expression of the GABA(A) alpha6 subunit via a cAMP-mediated pathway and that cAMP-coupled receptors for other neurotransmitters may similarly influence GABA(A) receptor subunit composition.

Animals↗