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Biomedical subjects

A Mukherjee

Publications and source records attributed to A Mukherjee.

At least 37 records · Page 2Linked to original sources

Residues of DDT and HCH pesticides in rice samples from different geographical regions of India: a multicentre study.

As part of a multicentre study conducted by the Indian Council of Medical Research, 2000 samples of rice were collected from rural and urban areas of 13 states representing different geographical regions of India. The samples were analyzed for residues of DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and different isomers of HCH [1,2,3,4,5,6-hexachlorocyclohexane, a mixture of isomers] by gas-chromatography. Residues of DDT and HCH, respectively, were detected in about 58 and 73% of the samples analysed. Medians of both DDT and HCH in rice samples were around 0.01 mg kg (-1). Concentrations of alpha-, beta-, gamma- and delta-HCH exceeded a maximum residue limit of 0.05 mg kg (-1) for each isomer in rice fixed by the Ministry of Health and Family Welfare of the Indian Government in 4.3, 2.6, 1.7 and 1.2% of the samples, respectively. There is no statutory limit fixed in India for DDT residues in cereals. Its maximum residue limit of 0.1 mg kg (-1) in cereals recommended by Codex was exceeded by about 2% of the samples examined. Estimated intake of DDT and isomers of HCH through consumption of rice contaminated at their median and 90th percentiles constituted a small proportion of their acceptable daily intakes.

Chromatography, Gas↗

Bioevaluation of radioactive bandages in a murine model of melanoma.

PURPOSE: To study the effectiveness of a radioactive bandage incorporating a beta(-) emitter for the treatment of superficial tumours like melanoma. MATERIALS AND METHODS: (188)Re tin particles were immobilized on a bandage patch ((188)Re bandage). The effectiveness of the (188)Re bandage for controlling tumour growth was tested in C57BL/6 mice bearing BL6/FIO melanoma. The effect of the single dose delivered, two-dose treatment and time of contact of bandages on the skin was studied by following tumour size. RESULTS: Tumour growth was delayed significantly in treated animals compared with controls. Complete tumour regression was observed with some doses of radiation. Histology studies and dose-rate calculations were also carried out to evaluate the effectiveness of (188)Re bandages. CONCLUSIONS: Radioactive bandages could be a promising modality for the treatment of skin cancers.

Animals↗

Parasite detection in patients with post kala-azar dermal leishmaniasis in India: a comparison between molecular and immunological methods.

AIMS: To evaluate the sensitivity and specificity of serological, immunohistochemical, and molecular methods in the diagnosis of post kala-azar dermal leishmaniasis (PKDL). METHODS: Twenty five patients with confirmed PKDL and 25 controls were included in the study. G2D10, a monoclonal antibody against Leishmania, was used for the immunohistochemical (IHC) staining of lesion sections to visualise anti-Leishmania donovani antibodies. The diagnostic usefulness of IHC was compared with enzyme linked immunosorbent assay (ELISA) with a recombinant (rk39) antigen, and a species specific polymerase chain reaction (PCR) assay, amplifying a kinetoplast minicircle DNA sequence. RESULTS: IHC detected 22 of 25 PKDL cases, giving a sensitivity of 88%. The diagnostic sensitivity of both the ELISA and PCR tests was higher (96%). All of the 25 controls examined were negative in PCR, indicating 100% specificity of the test, whereas ELISA showed 96% specificity. CONCLUSIONS: IHC with G2D10 significantly enhances the sensitivity of detection of PKDL over routine haematoxylin and eosin staining. ELISA with a recombinant antigen is an economical and practical assay. PCR is the most sensitive and specific diagnostic method for PKDL. The tests described would facilitate the recognition of patients with PKDL, enabling timely treatment, which would contribute greatly to the control of kala-azar.

Adolescent↗

Ultra-structural observations on the lymphoid organs of the freshwater catfish, Clarias batrachus (Linnaeus).

Light microscopic and ultra-structural studies of the lymphoid tissues such as blood immunocytes, spleen and pronephros of the freshwater catfish, Clarias batrachus, were carried out. The peripheral blood showed nucleated erythrocytes, total leucocytic count (TLC) more than that observed in mammalian blood and leucocytes with morphological appearance similar to the mammalian white blood cells (WBCs). The spleen and pronephros showed presence of numerous lymphocytes, monocytes and nucleated red blood cells (RBCs) along with hemosiderin-containing macrophages. The morphology of lymphoid organs of the catfish has been discussed in light of the evolution of the immune system in this class of vertebrates.

Animals↗

Vertigo and dizziness--a clinical approach.

Dizziness is a term which is used to describe a variety of sensations. It is possible to group these complaints into four types: a rotational sensation (Type I dizziness), impending faint (Type II dizziness), dysequilibrium (Type III dizziness) and vague lightheadness (Type IV dizziness). Type I dizziness or vertigo is due to disease of the vestibular system--peripheral or central, and is characterized by a feeling of movement relative to one's surrounding. The majority of dizzy patients, however, belong to Types II, III and IV, collectively called the non-vestibular system disorders. The distinction is usually possible by a detailed history and clinical examination, but some special bedside tests--the dizziness simulation battery--are often required for properly distinguishing the various types of dizziness. Important causes of vertigo and the non-vestibular system disorders have been discussed with focus on benign positional vertigo, acute peripheral vestibulopathy, Menieres' disease, toxic damage to labyrinths, perilymph fistula, cerebrovascular disease, multiple sclerosis, cerebellopontine angle tumors, basilar migraine, vestibular epilepsy, cervical vertigo and phobic postural vertigo.

Diagnosis, Differential↗

Severe inhibition of fusion by quasifission in reactions forming 220Th.

Evaporation residue cross sections have been measured following the fusion of 16O with 204Pb, forming the compound nucleus 220Th. These are compared with existing data for the same compound nucleus formed following fusion reactions with 40Ar, 48Ca, 82Se, and 124Sn projectiles. At energies where the reduced cross sections of xn evaporation residues would be expected to be the same for all reactions, those for the heavier projectiles are typically a factor of 10 smaller than those for 16O. This inhibition is attributed to strong competition of quasifission with fusion at the low angular momenta associated with evaporation residue formation.

Journal Article↗

Ionic self-diffusion in concentrated aqueous electrolyte solutions.

A self-consistent microscopic theory is developed to understand the anomalously weak concentration dependence of ionic self-diffusion coefficient D(ion) in electrolyte solutions. The self-consistent equations are solved by using the mean spherical approximation expressions of the static pair correlation functions for unequal sizes. The results are in excellent agreement both with the known experimental results for many binary electrolytes and also with the new Brownian dynamics simulation results. The calculated velocity time correlation functions also show quantitative agreement with simulations. The theory also explains the reason for observing different D(ion) in recent NMR and neutron scattering experiments.

Journal Article↗

Preparation and evaluation of 90 Y skin patches for therapy of superficial tumours in mice.

90Y, a beta emitting radionuclide, was immobilized in a bandage patch for possible application for the therapy of superficial maladies such as tumours and skin cancers. The aim was to prepare a radiation source that could deliver uniform dose within a short duration and avoid the inconveniences faced with the gamma sources used in teletherapy and brachytherapy. 90Y-ferric hydroxide macroaggregates were prepared, filtered and immobilized between two layers of gauze. When placed in saline, no radioactivity leached for 3 days, proving its safety for external application. Fibrosarcoma was induced in mice for checking the efficacy of 90Y patches. 90Y patches of various activities were prepared and applied on the tumours. The effect of time gap between inception and treatment of tumour, dose delivered and multiple application in fractionated doses was studied. In all the cases, tumour growth in the treated animals was considerably reduced in comparison with controls. It was concluded from the experiments that treatment should be started at the earliest stage possible, i.e. when the tumour is palpable. Delivery of dose from radioactive patches of approximately 90-100 MBq each, thrice at weekly intervals proved to be more effective for regression of tumour growth.

Animals↗

Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced rheumatoid arthritis.

BACKGROUND: The art of transplant surgery has gone a long way in establishing itself as an important discipline in medicine with the support of molecular biology, immunology, biochemistry, etc., as the ultimate treatment for the restoration of function of a failing organ. With the progressive increase in the life expectancy of human beings, there is an increasing discrepancy in the demand and supply of organ grafts. A less efficient alternative could be synthetic or mechanical grafts. Nucleated cell therapy, that is, cellular transplant, is a promising new area of study with its proven efficacy in neuro-degenerative disorders, hematopoietic disorders, diabetes and trauma-induced tissue loss, to name a few. Human fetal cell/tissue with its intrinsic hypo-antigenic advantage (up to 20 weeks of study), could be an interesting area of cellular/tissue transplant. Our research group has earlier reported on the safe use of umbilical cord whole blood and the successful transplant of a human fetal lung, heart, pancreas, liver, thymus, in an artificially prepared vascular subcutaneous axillary fold in which there was no feature of hyper-acute, acute or chronic rejection of the graft in HLA- and sex-randomized adult recipients, without concomitant immunosuppressives or radiation of the host to potentiate the survival of the fetal graft (within 20 weeks of gestation) within the lowest observation period of one month. The present study was aimed at examining the role of developing fetal adrenal transplants for patients with rheumatoid arthritis and severe pain due to involvement of inflammatory and neuropathic components. MATERIALS AND METHOD: Ten cases were enrolled in the present study after thorough informed consent and approval by the ethical committee of the institute. The age of the patients varied from 50 to 76 years and the group was comprised of three males and seven females. The age of the adrenal grafts varied from 16 to 20 weeks and these were collected from mothers admitted for hysterotomy and ligation. These long-standing rheumatoid patients (suffering for five to 15 years), presented with at least four of the seven 1987 revised criteria of the American College of Rheumatology for diagnosis of rheumatoid arthritis. A 2.5 cm long and 2 cm deep tissue space was dissected and prepared in each transplant recipient at the axilla using diathermy and knife after infiltrating the site with one percent lignocaine solution. The tissue collected from the consenting mother undergoing hysterotomy and ligation was inserted into this site, and the site was closed with 00 atraumatic vicryl. All necessary pre- and postoperative surgical precautions were taken to prevent infections. Sequential total count and differential count of leucocytes were undertaken to analyze the impact of the transplant on the host. After one month, a part of the transplanted fetal tissue was recovered for histological staining to examine whether there was any graft versus host reaction. RESULTS AND ANALYSIS: All ten patients tolerated the transplant procedure well. There was no fever, intractable pain or any other specific serious side-effect which could justify the removal of the transplant before one month. There was no discharge from the incision site and the healing of the scar was by and large normal. There was no unusual leucocytosis, lymphocytosis and the retrieved graft tissue did not suggest transplant rejection. However, there was definite pain relief, reduction in swelling and improvement of mobility of varying degree in a majority of the patients which was perceivable from the 15th day onwards. There was also a sense of well being (in 80%) and a gain in weight of three pounds or more (in 70%) among the fetal transplant recipients. DISCUSSION AND CONCLUSION: To understand the underlying mechanism, in case of pregnancy immunotolerance, we are of the opinion that emphasis should be placed on the role of non-specific and non-cytopathic blocking antibodies produced during pregnancy. The hypo-antigenicity of the developing human fetal system may possibly contribute to the production of this blocking antibody during pregnancy, and thus may play a role in the lack of recognition by the host's HLA system. This behaviour of the developing human fetal tissue provides some advantages over adult tissue for fetal cell/tissue transplantation purposes. The relief of pain, inflammation and restoration of mobility may be due to the effect of the transplanted adrenal graft, with the medullary component contributing to endorphin-like substance liberation and the cortical component contributing to glucocorticoid synthesis.

Adrenal Glands↗

Reentrant behavior of relaxation time with viscosity at varying composition in binary mixtures.

In order to understand the long known anomalies in the composition dependence of diffusion and viscosity of binary mixtures, we introduce here two new models and carry out extensive molecular dynamics simulations. In these models, the two molecular species (A and B) have the same diameter and mass. In model I the interspecies interaction is more attractive than that between the pure components, while the reverse is true for model II. Simulations and mode coupling theory calculations reveal that the models can capture a wide variety of behavior observed in experiments, including the reentrant viscosity dependence of relaxation time.

Journal Article↗

Homology modeling using multiple molecular dynamics simulations and docking studies of the human androgen receptor ligand binding domain bound to testosterone and nonsteroidal ligands.

To facilitate the rational design of novel and more potent androgen receptor ligands, three-dimensional models for the human androgen receptor ligand binding domain bound to testosterone have been developed. These models of the androgen receptor were based on the crystal structure of the highly homologous human progesterone receptor ligand binding domain. The homology modeled androgen receptor was refined using unrestrained multiple molecular dynamics simulations in explicit solvent. Key H-bonding partners with the 17-hydroxy group and 3-keto group of testosterone are Asn705 and Thr877, and Gln711 and Arg752, respectively. These models show the presence of a unique unoccupied cavity within the androgen receptor binding pocket which may be valuable in the development of novel selective androgen receptor ligands. A qualitative analysis of amino acid mutations within the hAR binding pocket that affect ligand binding are consistent with these androgen receptor models. In addition to testosterone, the binding modes of several hydroxyflutamide-like nonsteroidal ligands for the androgen receptor are investigated using flexible docking with FlexX followed by refinement of the initial complexes with molecular dynamics simulations. These docking studies indicate that Asn705 is an important determinant in binding hydroxyflutamide and its derivatives by participating in H-bond interactions with the alpha-hydroxy moiety of these ligands. In addition, the nitro functionality mimics the 3-keto group of the natural ligand testosterone and is involved in H-bonding interactions with Gln711 and Arg752. From these docking studies, we suggest a mechanism for the enantioselective binding of chiral hydroxyflutamide derivatives and expand upon the previously reported structure-activity relationship for hydroxyflutamide and its derivatives.

Amino Acid Substitution↗

Analysis of the subsite specificity of rat insulysin using fluorogenic peptide substrates.

Recombinant rat insulysin was shown to cleave the internally quenched fluorogenic peptide 2-aminobenzyl-GGFLRKVGQ-ethylenediamine-2,4-dinitrophenol at the R-K bond, exhibiting a K(m) of 13 microm and a V(max) of 2.6 micromol min(-1) mg(-1). Derivatives of this peptide in which the P(2) leucine or the P(2)' valine were replaced with other residues were used to probe the subsite specificity of the enzyme. Varying the P(2) residue produced a 4-fold range in K(m) and a 7-fold range in k(cat). The nature of the P(2) residue had a significant effect on the site of cleavage. Leucine, isoleucine, valine, and aspartate produced cleavage at the R-K bond. Asparagine produced 36% cleavage at the N-R bond and 64% cleavage at the R-K bond, whereas with alanine or serine the A-R and S-R bonds were the major cleavage sites. With tyrosine, phenylalanine, methionine, or histidine representing the varied residue X, cleavages at F-X, X-R, and R-K were seen, whereas with tryptophan equal cleavage occurred at the F-W and W-R bonds. Variable P(2)' residues produce less of a change in both K(m) and k(cat) and have little influence on the cleavage site. Exceptions are phenylalanine, tyrosine, leucine, and isoleucine, which in addition to producing cleavage at the R-K bond, produce significant cleavage at the L-R bond. Alanine and tyrosine were unique in producing cleavage at the F-L bond. Taken together, these data suggest that insulysin specificity is directed toward the amino side of hydrophobic and basic residues and that the enzyme has an extended substrate binding site.

Amino Acid Sequence↗

Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways.

Tumor necrosis factor-alpha (TNF) and the ligand for receptor activator of NF-kappaB (RANKL) are abundant in sites of inflammatory bone erosion. Because these cytokines are potent osteoclastogenic factors and because their signaling pathways are considerably overlapping, we postulated that under pro-inflammatory conditions RANKL and TNF might synergistically orchestrate enhanced osteoclastogenesis via cooperative mechanisms. We found TNF, via TNF type 1 receptor (TNFr1), prompts robust osteoclastogenesis by osteoclast precursors pretreated with RANKL, and deletion of TNFr1 abrogates this response. Enhanced osteoclastogenesis is associated with high expression of otherwise TNF and RANKL-induced mediators, including c-Src, TRAF2, TRAF6, and MEKK-1, levels of which were notably reduced in TNFr1 knockouts. Recruitment of TRAFs and MEKK1 leads to activation of downstream pathways, primarily I kappa B/NF-kappa B, ERKs, and cJun/AP-1. Consistent with impaired osteoclastogenesis and reduced expression of TRAFs and MEKK1, we found that phosphorylation and activation of I kappa B, NF-kappa B, ERKs, and cJun/AP-1 are severely reduced in RANKL-treated TNFr1-null osteoclast precursors compared with wild type counterparts. Finally, we found that TNF and RANKL synergistically up-regulate RANK expression in wild type precursors, whereas basal and stimulated levels of RANK are significantly lower in TNFr1 knockout cells. Our data suggest that exuberant TNF-induced osteoclastogensis is the result of coupling between RANK and TNFr1 and is dependent upon signals transmitted by the latter receptor.

Animals↗

Preparation and studies with 90Y-labelled particles for use in radiation synovectomy.

90Y-FHMA (Ferric hydroxide macroaggregates) and 90Y-HA (hydroxyapatite) were prepared in >95% yield using 90Y from an in-house 90Sr-90Y generator. Most of the particles ranged from 5 to 20 microm in diameter and retained radiochemical purity > 95% in human serum for at least 7 days at 37 degrees C. Gamma camera imaging of normal rabbits after intraarticulation of the particles showed complete retention of activity within the knee cavity with no measurable radioactivity leaching out of the joints over a 96 hour period.

Animals↗