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Biomedical subjects

S Mondal

Publications and source records attributed to S Mondal.

At least 19 recordsLinked to original sources

Doppler effect in fluorine K-Auger line produced in electron-induced core ionization of SF6.

An experimental evidence is reported on the observation of the Doppler effect in fluorine K-Auger line emitted from a core-ionized SF6 molecule under an impact of 16 keV electrons. The emitting source of the Auger line is found to acquire a kinetic energy of 4.7+/-0.3 keV. We propose that such large energy is released from the Coulomb repulsion taking place between F+ and SF5+ fragment ions under influence of an intense focusing field of the incident electrons. In the presence of the Coulomb field of these ions, the Auger line obtains a polarization P = 76%+/-7%.

Journal Article↗

Analysis of molecular alterations in chromosome 8 associated with the development of uterine cervical carcinoma of Indian patients.

OBJECTIVES: We have been done the detailed deletion mapping of chromosome (chr.) 8p21.3-23 to localize the candidate tumor suppressor gene(s) (TSGs) loci as well as studied the mechanism of activation of c-myc gene, located at chr.8q24.1, by analyzing the amplification/rearrangement/HPV integration within approximately 580 kb of c-myc locus in uterine cervical carcinoma (CaCx) of Indian patients. The association between the deletions in chr.8p21.3-23 and alterations in the c-myc locus has also been analyzed. METHODS: The deletion mapping of chr.8p21.3-23 was done by 15 microsatellite markers and the alterations in the c-myc locus were analyzed by Southern hybridization using the pal-1/c-myc/mlvi-4/HPV 16/18 probes in seven cervical intraepithelial neoplasia (CIN) and 55 primary uterine cervical carcinoma. The alterations in chr.8p/q have been correlated with the different clinicopathological parameters. RESULTS: Three discrete minimal deleted regions with high frequencies of loss of heterozygosity (LOH) (37-43%) were identified in the chr.8p23.1-23.2 (D1), 8p23.1 (D2), and 8p 21.3-22 (D3) regions within 0.41-4.62 Mb. The deletion in the D1 region was significantly associated with the deletion in the D2 region (P = 0.03), whereas the deletion in D2 was marginally associated with the deletion in the D3 region (P = 0.07). The alterations in the c-myc locus were seen in 43% of the samples. About 35% of the samples showed coalterations in both arms of chr.8. No significant association was observed with the alterations in chr.8p/q as well as with the different clinicopathological parameters. CONCLUSIONS: The deletions in chr.8p21.3-23 and the alterations in the c-myc locus are independently associated with the development of CaCx. The D1-D3 regions in chr.8p21.3-23 could harbor candidate TSGs associated with the development of this tumor. The c-myc gene was activated by amplification/rearrangement at the pal-1/c-myc/mlvi-4 loci as well as HPV integration in the pal-1 locus in this tumor.

Adult↗

Peripheral plasma FSH concentration in relation to expression of estrus in Sahiwal cattle (Bos indicus).

An experiment was conducted to investigate the changes in peripheral plasma FSH concentrations in relation to expression of estrus in Sahiwal cows. Out of total five estrus, three were accompanied by overt signs whereas rest two were silent estrus. In cows with overt estrus, plasma FSH concentrations during periestrus, early luteal, midluteal and late luteal phase were 1.65+/-0.34, 1.67+/-0.21, 1.58+/-0.18 and 1.69+/-0.31 ng/ml, respectively and the corresponding values in cows with silent estrus being 0.68+/-0.39, 0.50+/-0.12, 0.75+/-0.13 and 0.46+/-0.12 ng/ml, respectively. The overall plasma FSH levels in cows that exhibited overt estrus was 1.63+/-0.82 ng/ml as against 0.64+/-0.55 ng/ml in silent estrus. It was concluded that FSH levels were higher (P<0.01) in cows that exhibited overt estrus compared to silent estrus.

Animals↗

Peripheral plasma progesterone concentration in relation to estrus expression in Sahiwal cows.

The present study investigated the changes in peripheral plasma progesterone levels in relation to expression of estrus in Sahiwal cows. Out of a total of five estrus, three were accompanied by overt signs whereas the remaining two were silent estrus. In cows with overt estrus, plasma progesterone concentrations during periestrus, early luteal, midluteal and late luteal phase were 0.40 +/- 0.02, 0.74 +/- 0.10, 1.94 +/- 0.22 and 0.63 +/- 0.16 ng/ml, respectively and the corresponding values in cows with silent estrus being 0.47 +/- 0.03, 0.94 +/- 0.08, 1.39 +/- 0.13 and 0.95 +/- 0.19 ng/ml, respectively. The overall plasma progesterone levels in cows that exhibited overt estrus was 1.23 +/- 0.99 ng/ml as against 1.08 +/- 0.09 ng/ml in silent estrus. It was concluded that progesterone levels were lower (P > 0.05) in cows that exhibited silent estrus compared to overt estrus.

Animals↗

Gramicidin A and its complexes with Cs+ and Tl+ ions in organic solvents. A study by steady state and time resolved emission spectroscopy.

Gramicidin A (gr A), a linear pentadecapeptide containing four trp residues has been studied using steady state and time resolved fluorescence (at 298 K) and phosphorescence (at 77 K) in methanol (CH3OH), ethanol (C2H5OH), dimethyl sulfoxide (DMSO), 1,4-dioxane, 2-methyl tetrahydrofuran (2-MeTHF), ethanol/benzene (C2H5OH/C6H6) mixed solvent. Similar studies have also been carried out in CH3OH containing monovalent cations K+, Cs+, Tl+ and divalent cation Ca2+. Lambda(max) of fluorescence is found to be a good signature of the different forms having double helical structure [dh (1) to dh (4)] (J. Struct. Biol. 121 (1998) 123-141). Steady state and time resolved quenching studies of gr A by KI in CH3OH and DMSO and life time of the emitting singlet states of gr A support that gr A exists as a mixture of different forms of double helical (dh) structure [dh (1) to dh (4)] in CH3OH and as a random coil structure in DMSO. This study further indicates that emitting trp residue in DMSO is better shielded than that in CH3OH. Phosphorescence spectra of gr A at 77 K in CH3OH glass suggests that gr A retains a particular conformation dh (3) in this matrix. The phosphorescence spectra of gr A [conformation dh (4)] in 2-MeTHF at 77 K is further red shifted indicating that among all the dh forms, dh (4) has the emitting trp residue in most hydrophobic environment. The hydrophobicity of the emitting tryptophan environment is thus found to be in the order: dh (1)<dh (3)<dh (4). Since 2-MeTHF forms a clear glass at low temperature, it is thus possible to study the side chain arrangement of gr A dh (4) as a function of temperature. The phosphorescence spectra in different alcohol glassy matrix are in conformity with the observation of different side chain arrangement of gr A as one changes the polarity of alcohol. Steady state and time resolved quenching studies of gr A using Cs+ ion in CH3OH at 298 K clearly demonstrate the two binding sites for the metal ions and provide the value of equilibrium constant of the 'non-emitting' complex of gr A with Cs+ ion in the ground state. The observation of distinct red shift of the (0,0) band of the phosphorescence spectra of the complexes of gr A with K+, Cs+ and Tl+ ions at 77 K compared to that in CH3OH glass confirms the metal ion induced change of conformation in dh (3). The result also suggests that the emitting trp residues in the complexes are in somewhat more hydrophobic environment compared with that in the free gr A in CH3OH glass. The triplet state life time of these complexes indicate that the heavy metal ions Cs+ and Tl+ are within a Van der Waal's distance of emitting trp residue in gr A in CH3OH glass at 77 K so that they are capable of inducing increased spin-orbit coupling due to a heavy atom effect.

Cations, Monovalent↗

In vitro effect of temperature on phagocytic and cytotoxic activities of splenic phagocytes of the wall lizard, Hemidactylus flaviviridis.

The in vitro effect of temperature on phagocytosis, nitric oxide production and interleukin-1 (IL-1) secretion by splenic phagocytes isolated from the wall lizard (Hemidactylus flaviviridis) demonstrated that changes in temperature altered non-specific defenses. The LPS-induced percentage phagocytosis and phagocytic index were recorded maximum at 25 degrees C. The phagocytic activity declined considerably when the phagocytes were incubated at low (7 and 15 degrees C) or high (37 degrees C) temperatures. The presence of bacterial lipopolysaccharide (LPS) in the incubation medium could considerably enhance the phagocytic activity of splenic phagocytes. A similar temperature-related effect was also observed on LPS-induced cytotoxic activity of phagocytes. LPS could stimulate the nitrite release indicating nitric oxide production only at 25 degrees C. Likewise, the proliferative responses of immature rat's thymocytes to LPS-induced phagocyte-conditioned medium suggest that IL-1 secretion was enhanced when phagocytes were cultured at 25 degrees C. This suggests that 25 degrees C is the optimal temperature for phagocyte functions in H. flaviviridis. The decrease or increase in temperature other than at 25 degrees C dramatically suppressed the phagocyte activities.

Animals↗

The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth.

The unique INK4A/ARF locus at chromosome 9p21 encodes two distinct proteins that intimately link the pRB and p53 tumour suppressor pathways. p16INK4A has been identified as an inhibitor of the cell cycle, capable of inducing arrest in G1 phase. p14/p19ARF on the other hand can induce both G1 and G2 arrest due to its stabilizing effects on the p53 transcription factor. In addition to their roles in growth arrest, both proteins are involved in cellular senescence and apoptosis. The frequent mutation or deletion of INK4A/ARF in human tumours as well as the occurence of tumours in the murine knockout models have identified both p16 and ARF as bona fide tumour suppressors.

Animals↗

Tracking the invasiveness of human astrocytoma cells by using green fluorescent protein in an organotypical brain slice model.

OBJECT: Although it is known that malignant astrocytomas infiltrate diffusely into regions of normal brain, it is frequently difficult to identify unequivocally the solitary, invading astrocytoma cell in histopathological preparations or experimental astrocytoma models. The authors describe an experimental system that facilitates the tracking of astrocytoma cells by using nonneoplastic cerebral tissue as the substrate for invasion. METHODS: Cerebral tissue was cut into 1-mm-thick slices and cultured in the upper chamber of a Transwell culture dish on top of a polyester membrane (0.4-mm pore size) that was bathed in medium supplied by the lower chamber. Two astrocytoma cell lines, U-87 MG (U87) and U343 MG-A (U343), were selected because of their differing basal cell motilities in monolayer cultures. The astrocytoma cells were stably transfected with vectors that expressed green fluorescent protein (GFP), either alone or as a fusion protein with the receptor for hyaluronic acid-mediated motility (RHAMM) in either sense or antisense orientations. Stably transfected clones that had high levels of GFP expression were selected using the direct visualization provided by fluorescence microscopy and fluorescence-activated cell-sorter analysis. The GFP-expressing astrocytoma cell clones were implanted into the center of the brain slice and the degree of astrocytoma invasion into brain tissue was measured at different time points by using the optical sectioning provided by the confocal laser microscope. The authors observed that GFP-expressing astrocytoma cells could be readily tracked and followed in this model system. Individual astrocytoma cells that exhibited green fluorescence could be readily identified following their migration through the brain slices. The GFP-labeled U87 astrocytoma cells migrated farther into the brain slice than the U343 astrocytoma cells. The RHAMM-transfected GFP-labeled astrocytoma cells also infiltrated farther than the GFP-labeled astrocytoma cells themselves. The expression of antisense RHAMM virtually abrogated the invasion of the brain slices by both astrocytoma cell lines. CONCLUSIONS: The authors believe that this organotypical culture system may be of considerable utility in studying the process of astrocytoma invasion, not only because it provides a better representation of the extracellular matrix molecules normally encountered by invading astrocytoma cells, but also because the GFP tag enables tracking of highly migratory and invasive astrocytoma cells under direct vision.

Astrocytoma↗

Relation between plasma leptin and anthropometric and metabolic covariates in lean and obese diabetic and hyperlipidaemic Asian Northern Indian subjects.

This study investigated the relationship of plasma leptin to obesity, diabetes and hyperlipidaemia in Asian Northern Indian subjects, considered to have a predisposition to abdominal obesity and metabolic syndrome. A total of 72 subjects, subcategorised into lean and obese healthy subjects, lean and obese Type 2 diabetic and lean and obese non-diabetic hyperlipidaemic subjects were recruited. High leptin values were observed in all obese groups, and obese diabetic patients showed the highest levels. In lean and obese diabetic subjects, plasma leptin did not show any correlation to any index of glycaemia. When all lean and all obese subjects were analysed in two separate groups, body mass index (BMI), percent total body fat, and body density significantly correlated with the plasma leptin levels (p<0.05). Leptin values, when correlated to all variables in all patients taken together, showed the greatest magnitude of correlation with BMI (r=0.64), percent total body fat (r=0.67), and waist circumference (r=0.51). Strong inverse correlation was seen with body density (r=-0.67). Levels of serum insulin did not show any correlation with leptin levels in all subjects combined, and separately in various groups. Multiple linear regression analysis performed in obese, non-diabetic and normolipidaemic subjects, all Type 2 diabetic and all non-diabetic hyperlipidaemic subjects separately showed that percent total body fat is the only significant predictor of plasma leptin concentration in all the 3 groups. The present study suggests that plasma leptin has a strong positive correlation with percent total body fat in Asian Northern Indian subjects. Among other components of metabolic syndrome, only abdominal obesity is weakly correlated to serum leptin levels.

Adipose Tissue↗

Suppression of Ehrlich subcutaneous solid tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype antibody.

Mice vaccinated with purified Ehrlich tumor-plasma GT1b admixed with Freund's adjuvant suppressed subcutaneous growth of the same tumor cells inoculated in vivo by 37.9%. The suppression was dose-dependent and was a result of humoral immune response against GT1b. Further, when mice were injected with varying doses of rabbit polyclonal anti-GT1b IgM antibody and challenged with Ehrlich tumor cells subcutaneously, a significant reduction in tumor growth (47.3%) was observed. Again, the suppression was dose-dependent. To strengthen furthier the observed therapeutic potential of this immunogenic GT1b, mice were immunized with anti-idiotype antibodies to GT1b raised in female Sprague Dawley rats by immunization with rabbit anti-GT1b IgM, which is expected to carry the structural image of GT1b. Immunization of mice with this anti-idiotype antibody was observed to suppress Ehrlich subcutaneous solid tumor growth by 60%. The results indicated therapeutic potential of immunogenic tumor-associated ganglioside in solid tumor model.

Animals↗

Expression of p57(KIP2) potently blocks the growth of human astrocytomas and induces cell senescence.

Astrocytic tumors frequently exhibit defects in the expression or activity of proteins that control cell-cycle progression. Inhibition of kinase activity associated with cyclin/cyclin-dependent kinase co-complexes by cyclin-dependent kinase inhibitors is an important mechanism by which the effects of growth signals are down-regulated. We undertook the present study to determine the role of p57(KIP2) (p57) in human astrocytomas. We demonstrate here that whereas p57 is expressed in fetal brain tissue, specimens of astrocytomas of varying grade and permanent astrocytoma cell lines do not express p57, and do not contain mutations of the p57 gene by multiplex-heteroduplex analysis. However, the inducible expression of p57 in three well-characterized human astrocytoma cell lines (U343 MG-A, U87 MG, and U373 MG) using the tetracycline repressor system leads to a potent proliferative block in G(1) as determined by growth curve and flow cytometric analyses. After the induction of p57, retinoblastoma protein, p107, and E2F-1 levels diminish, and retinoblastoma protein is shifted to a hypophosphorylated form. Morphologically, p57-induced astrocytoma cells became large and flat with an expanded cytoplasm. The inducible expression of p57 leads to the accumulation of senescence-associated beta-galactosidase marker within all astrocytoma cell lines such that approximately 75% of cells were positive at 1 week after induction. Induction of p57 in U373 astrocytoma cells generated a small population of cells ( approximately 15%) that were nonviable, contained discrete nuclear fragments on Hoechst 33258 staining, and demonstrated ultrastructural features characteristic of apoptosis. Examination of bax and poly-(ADP ribose) polymerase levels showed no change in bax, but decreased expression of poly-(ADP ribose) polymerase after p57 induction in all astrocytoma cell lines. These data demonstrate that the proliferative block imposed by p57 on human astrocytoma cells results in changes in the expression of a number of cell cycle regulatory factors, cell morphology, and a strong stimulus to cell senescence.

Apoptosis↗

Molecular biology and neurosurgery in the third millennium.

The application of techniques in molecular biology to human neurosurgical conditions has led to an increased understanding of disease processes that affect the brain and to novel forms of therapy that favorably modify the natural history of many of these conditions. Molecular strategies are currently being either used or sought for brain tumors, stroke, neurodegenerative diseases, vascular malformations, spinal degenerative diseases, and congenital malformations of the central nervous system. Considering that the structure of deoxyribonucleic acid was ascertained by Watson and Crick as recently as 1953, the progress that has been made to implement molecular medicine in clinical practice has been meteoric. More than 2000 patients have been treated in approved gene therapy trials throughout the world. Many of these patients have been treated for neurological diseases for which conventional medical therapies have been of limited utility. As part of this continuing series on advances in neurosurgery in the third millennium, we first reflect on the history of the nascent field of molecular biology. We then describe the powerful techniques that have evolved from knowledge in this field and have been used in many publications in Neurosurgery, particularly within the past decade. These methods include commonly used techniques such as advanced cytogenetics, differential display, microarray technology, molecular cell imaging, yeast two-hybrid assays, gene therapy, and stem cell utilization. We conclude with a description of the rapidly growing field of bioinformatics. Because the Human Genome Project will be completed within 5 years, providing a virtual blueprint of the human race, the next frontier (and perhaps our greatest challenge) will involve the development of the field of "proteomics," in which protein structure and function are determined from the deoxyribonucleic acid blueprint. It is our conviction that neurosurgeons will continue to be at the forefront of the treatment of patients with neurological diseases using molecular strategies, by performing essential research leading to increased understanding of diseases, by conducting carefully controlled studies to test the effects of treatments on disease processes, and by directly administering (by neurosurgical, endovascular, endoscopic, or stereotactic means) the treatments to patients.

Cytogenetics↗

Correlation of level of gangliosides in plasma with cancer in human patients.

Levels of gangliosides in the plasma of human patients with cancers of the breast, cheek, oesophagus, rectum, penis, bladder and skin, as analysed by thin layer chromatography and quantitative densitometric scanning, were found to increase many fold (ranging from 3.5 to 5.96 folds), compared to that of normal individuals. The ganglioside levels in the plasma of patients with benign tumors were comparable to that of normal individuals, thus suggesting correlation between increased ganglioside levels in the plasma and malignant growth in cancer patients. These increased levels of gangliosides in the plasma of Ca-breast, Ca-cheek and Ca-penis gradually increased with the advancement of the disease and showed some correlation with the increase in stage of the disease. The levels of gangliosides in the plasma of patients with Ca-breast and Ca-cheek were found to decrease significantly after surgical removal of the primary cancerous growth. The results indicated diagnostic as well as prognostic significance of plasma ganglioside levels in human cancers.

Adult↗

Suppression of Ehrlich ascites tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype of the anti-GT1b IgM.

Ehrlich tumor expresses the ganglioside GT1b. The plasma of mice with Ehrlich ascites tumor burden also contains GT1b. The structural identity of plasma GT1b was ascertained by a series of enzymatic degradation and mass spectral analysis. Mice were vaccinated with purified plasma GT1b admixed with Freund's adjuvant (FA). Sixty nine percent suppression of Ehrlich ascites tumor growth was observed in vaccinated mice. The suppression was dose-dependent. It is hypothesized that the tumor growth-suppression is a result of immune response to GT1b Humoral immune response to GT1b was demonstrated by passive hemagglutination assay of the sera of vaccinated mice. To test the hypothesis, the mice were administered with rabbit polyclonal anti-GT1b IgM antibody in varying doses and challenged with Ehrlich tumor. A significant reduction in tumor growth (65%) was observed in mice administered with anti-GT1b IgM antibody. Again, the suppression was dose-dependent. To verify further, another batch of mice was immunized with anti-idiotypic antibodies to rabbit anti-GT1b IgM raised in rat. The polyclonal anti-idiotype antibody is expected to carry the structural image of GT1b. In a dose-dependent manner, a maximum of 82% suppression of tumor growth was observed in mice immunized with the anti-idiotype antibody. This observation further strengthened the hypothesis that ganglioside mediated suppression of tumor growth may be a result of immunogenicity of the target ganglioside. This was also supported by positive reaction of the sera of anti-idiotype vaccinated mice with both anti-idiotype antibody and ganglioside GT1b in passive hemagglutination assay. The results favour the therapeutic potential of immunogenic tumor-associated gangliosides.

Animals↗

Sexual dimorphism in phagocytic activity of wall lizard's splenic macrophages and its control by sex steroids.

The splenic macrophages of wall lizards exhibited marked sex-related difference in their phagocytic activity. The percentage phagocytosis and phagocytic index in females was considerably higher than that of males. Gonadectomy resulted in significant increase in percentage phagocytosis and phagocytic index in both male as well as female lizards, suggesting that gonadal hormones inhibit macrophage phagocytosis. This was further confirmed by dose and time-related in vivo and in vitro experiments in which DHT suppressed phagocytosis which increased with dose or duration of treatment, while E(2) either suppressed or had no effect on phagocytosis, depending on dose and duration of treatment. Exposure of macrophages to steroid receptor antagonists, cyproterone acetate (CPA), or tamoxifen citrate (Tam) prior to treatment with their respective sex steroids markedly reduced the DHT- or E(2)-modulated suppression of macrophage phagocytosis. It is concluded that the sex steroids modulate splenic macrophage phagocytosis via receptor-mediated systems.

Animals↗

Astrocytoma adhesion to extracellular matrix: functional significance of integrin and focal adhesion kinase expression.

Evidence is accumulating implicating a role for integrins in the pathogenesis of cancer, a disease in which alterations in cellular growth, differentiation, and adhesive characteristics are defining features. In the present report we studied a panel of 8 human astrocytoma cell lines for their expression of integrin subunits by RT-PCR, and of integrin heterodimers by immunoprecipitation analyses. The functionality of integrin heterodimers was assessed using cell attachment assays to plastic or single matrix substrates. Downstream effects of integrin activation were studied by western blot analyses of FAK expression in human astrocytoma cell lines growing on plastic and on a fibronectin matrix, and in 13 primary human brain tumor specimens of varying histopathological grade. Furthermore, we studied tyrosine phosphorylation of FAK in astrocytoma cells growing on plastic versus fibronectin. Finally, we analyzed the effects of intermediate filament gene transfer on FAK phosphorylation in SF-126 astrocytoma cells. Our data show that astrocytoma cell lines express various integrin subunits by RT-PCR, and heterodimers by immunoprecipitation analyses. The beta1 and alphav integrin subunits were expressed by all astrocytoma cell lines. The alpha3 subunit was expressed by all cell lines except SF-188. By immunoprecipitation, the fibronectin receptor (alpha5beta1 integrin heterodimer) and the vitronectin receptor (alphavbeta3) were identified in several cell lines. Astrocytoma cell attachment studies to human matrix proteins suggested that these integrin heterodimers were functional. Using confocal laser microscopy, we showed that FAK was colocalized to actin stress fibers at sites of focal adhesion complexes. By western blot, FAK was variably but quite ubiquitously expressed in human astrocytoma cell lines, and in several primary human astrocytoma specimens. When U373 and U87 MG astrocytoma cells bind to a fibronectin matrix, FAK is phosphorylated. GFAP-transfected SF-126 human astrocytoma cells were shown to overexpress the phosphorylated form of FAK only when these cells were placed on a fibronectin matrix. This result is of interest because it suggests that manipulations of the astrocytoma cytoskeleton per se can bring about potential signaling changes that channel through integrins and focal adhesion sites leading to activation of key kinases such as FAK.

Adult↗