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Biomedical subjects

M Anand

Publications and source records attributed to M Anand.

At least 19 recordsLinked to original sources

Searching for signatures of life on Mars: an Fe-isotope perspective.

Recent spacecraft and lander missions to Mars have reinforced previous interpretations that Mars was a wet and warm planet in the geological past. The role of liquid water in shaping many of the surface features on Mars has long been recognized. Since the presence of liquid water is essential for survival of life, conditions on early Mars might have been more favourable for the emergence and evolution of life. Until a sample return mission to Mars, one of the ways of studying the past environmental conditions on Mars is through chemical and isotopic studies of Martian meteorites. Over 35 individual meteorite samples, believed to have originated on Mars, are now available for lab-based studies. Fe is a key element that is present in both primary and secondary minerals in the Martian meteorites. Fe-isotope ratios can be fractionated by low-temperature processes which includes biological activity. Experimental investigations of Fe reduction and oxidation by bacteria have produced large fractionation in Fe-isotope ratios. Hence, it is considered likely that if there is/were any form of life present on Mars then it might be possible to detect its signature by Fe-isotope studies of Martian meteorites. In the present study, we have analysed a number of Martian meteorites for their bulk-Fe-isotope composition. In addition, a set of terrestrial analogue material has also been analysed to compare the results and draw inferences. So far, our studies have not found any measurable Fe-isotopic fractionation in bulk Martian meteorites that can be ascribed to any low-temperature process operative on Mars.

Biological Evolution↗

Childhood aplastic anaemia in Lucknow, India: incidence, organochlorines in the blood and review of case reports following exposure to pesticides.

OBJECTIVES: A hospital-based case-control study, the first in India, was conducted to determine the incidence of childhood aplastic anaemia in and around Lucknow in the backdrop of organochlorine levels in the blood and review the database for any association between the disease and exposure to pesticides. DESIGN AND METHODS: A total of 25 cases of childhood aplastic anaemia were identified as per established criteria and enrolled over the study period of 1 year. Their blood organochlorine levels were determined using a gas-liquid chromatograph equipped with an electron capture detector. RESULTS: The annual incidence of childhood aplastic anaemia in and around Lucknow was found to be 6.8 cases per million which is higher than many countries (e.g., France, Brazil, UK, and United States) but lower than those reported in Sweden, China and an European-Israeli collaborative study. Blood levels of alpha-HCH, gamma-HCH, delta-HCH, total-HCH, and p, p'-DDE were higher in children with aplastic anaemia than in those of controls; only alpha-HCH differed significantly (P < 0.05). CONCLUSIONS: Although this pilot study, with limited statistical power, did not support any association between exposure to organochlorines and risk of childhood aplastic anaemia, a possible association between the two could not be ruled out in view of several cases identified following exposure to pesticides.

Anemia, Aplastic↗

The presence of a BCR-ABL mutant allele in CML does not always explain clinical resistance to imatinib.

The expansion of a leukemia clone bearing a Bcr-Abl kinase domain mutation is associated with acquired resistance to imatinib and may also predict disease progression in patients with Philadelphia-positive chronic myeloid leukemia (CML). Here we report results of pyrosequencing to quantitate the non-mutated and mutant alleles in 12 CML patients monitored over periods ranging from 11 to 58 months, and describe three contrasting kinetic patterns: Group 1 - in four patients total BCR-ABL transcript numbers remained high with the mutant allele predominating; Group 2 - in four patients the total number of BCR-ABL transcripts fell to low levels but the mutant allele predominated; and Group 3 - in four other patients the total level of transcripts remained high (n = 2) or fell (n = 2) but the mutant clone persisted at relatively low level. In Group 2 the mutant leukemia clone was presumably still relatively sensitive to imatinib but in Group 1 the leukemia could be classified as resistant. In Group 3 patients the imatinib sensitivity of the leukemia was variable. We conclude that a mutant clone does not necessarily have a proliferative advantage and its presence does not always account for resistance to imatinib. Other mechanisms underlie resistance in at least some patients.

Adult↗

Lattice geometry, gap formation and scale invariance in forests.

The geometry of the lattice used in ecological modeling is important because of the local nature of ecological interactions. The latter can generate complex behavior such as criticality (scale-invariance). In this work, we implement two slightly different forest disturbance models on three lattices, each with square, triangular and hexagonal symmetry, in order to study the effect of geometry. We calculate the density distribution of gaps in a forest and find bumps in the distribution at sizes that depend on lattice geometry. Similar bumps were observed in real data but remained unexplainable. We suggest that these bumps provide information about the geometry and scale of ecological interactions. We also found an effect of geometry on the conditions under which criticality appears in model forests. These conditions appear to be more biologically realistic, and also linked to the likelihood of local disturbance propagation. The scaling exponent of the gap-size distribution, however, was found to be independent of both model and geometry, a hallmark of universality.

Demography↗

Biomonitoring of organochlorines in women with benign and malignant breast disease.

Established risk factors for breast cancer explain breast cancer risk only partially. Organochlorines are considered to be a possible cause for hormone-dependent cancers. A hospital-based case-control study, the first from India, was conducted among 50 women undergoing surgery for breast disease to examine the association between organochlorine exposure and breast cancer risk. Blood, tumor, and surrounding adipose tissue of the breast were collected from the subjects with benign (control) and malignant breast (study) lesions and analyzed to determine organochlorine insecticides using a gas-liquid chromatograph equipped with an electron capture detector. The alpha, beta, gamma, and delta isomers of hexachlorocyclohexane (HCH), p,p'-dichlorodiphenyltrichloroethane (DDT), o,p'-DDT, p,p-dichlorodiphenyldichloroethylene, and p,p'-dichlorodiphenyldichloroethane were frequently detected in three specimens. Total HCH and total DDT levels were higher in the blood of the study group (25 cases) than in those of the controls (25 cases) with only gamma-HCH being significantly different (P<0.05). However, both total HCH and total DDT were higher in the tumor tissues of the controls than in those of the study group; gamma-HCH was significantly different (P<0.05). The level of total HCH (alpha-HCH was significantly different, P<0.05) was higher in the breast adipose tissue of the study group, whereas total DDT was higher in the breast adipose tissue of the control group. The distribution of known confounders of breast cancer including age, body mass index, age at menarche and menopause, duration of breast feeding, and family history related to breast disease did not differ significantly between benign and malignant groups. This pilot study with limited statistical power does not support a positive association between exposure to organochlorines and risk of breast cancer but paves the way for a larger Indian study with greater statistical power encompassing different regions of the country to enable statistically sound conclusions.

Adipose Tissue↗

A model for the formation and lysis of blood clots.

Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183-218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.

Blood Coagulation↗

Gas mixing for achieving suitable conditions for single point aerosol sampling in a straight tube: experimental and numerical results.

Experimental measurements of velocity and tracer gas concentration are taken in a straight tube to evaluate the effectiveness of mixing in achieving conditions as required by ANSI N13.1-1999 for single point extractive sampling from stacks and ducts of nuclear facilities. Mixing is evaluated for inlet turbulent intensities of 1.5%, 10%, and 20%, achieved by introducing various bi-plane grids, and for conditions generated by a commercial static gas mixer. The data obtained (at Reynolds number = 15,000) highlight the importance of inlet turbulence intensity in the process of turbulent dispersion of a dilute gas. The gas mixer does not introduce significant pressure losses and unlike bi-plane grids, the turbulence downstream of the mixer is not homogenous. A judicious choice of the release location that uses the large scale eddies and inhomogeneity of the turbulence ensures that the specified ANSI N13.1-1999 criteria are attained within 7 diameters downstream of the duct inlet. This is significantly more effective than a bi-plane grid where even with 20% inlet intensity the criteria are met only at 21 diameters downstream. The predictions of a proposed semi-empirical correlation match favorably with data. For example, at 18 diameters downstream with inlet intensities of 1.5% and 10%, the predicted coefficients of variation (COVs) of 150% and 65% are close to the actual values of 154% and 50%; where the COV of a set of measurements is the ratio of the standard deviation of the set to its mean value. The corresponding results obtained using commercially available software are 141% and 12%. Results from a particle-tracking model show good qualitative trends, but they should not be used to determine compliance with the requirements of the ANSI standard.

Aerosols↗

Bone marrow metastasis in anaplastic oligodendroglioma.

Oligodendroglioma is a rare primary brain tumour. These tumours rarely metastasis extraneurally because of the absence of a lymphatic system, the presence of the blood-brain barrier and the patient's poor overall survival. Oligodendroglioma may spread via the cerebrospinal fluid or after surgical intervention. Metastasis to bone marrow is extremely rare. Oligodendroglioma is now considered a chemosensitive disease. If chemotherapy leads to prolonged survival, we may see more extraneural metastases in future.

Antineoplastic Agents↗

Neuropsychological studies on lead battery workers.

This study assessed the psychological status of 60 lead-acid battery workers occupationally exposed to low level lead and 30 referents in Lucknow. Digit spans and symbol, Bourdon-wiersma vigilance and Raven's Progressive matrices tests were administered. Significant impairments in concentration, attention, auditory and visual memory, psycho-motor speed, perceptual accuracy, and visual reasoning were observed in the workers compared to the referents. The deficits were not related to exposure duration since the magnitude of the impairments observed in workers with 1-y duration was the same as in those with more (up to 30 years) work duration. The blood lead of the battery workers was significantly elevated. There were functional deficits of the central nervous system in the lead-acid battery workers.

Adolescent↗

CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease.

The expression of CD40L was investigated in HD involved lymph nodes by flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR). Also an investigation of the role of CD40L in upregulation of the anti-apoptotic gene BclxL in a Hodgkin's disease (HD) derived cell line was undertaken. HD patients (n = 18) had significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment as compared to controls (n = 8). HD patients also demonstrated higher numbers of CD4+, CD8+ and CD19+ lymphocytes co-expressing CD40L as compared to controls. The CD40L signal was consistently and significantly upregulated in HD patients (n = 5) as compared to controls (n = 3) at the mRNA level. RT-PCR and FCM analysis revealed that soluble CD40L upregulated BclxL levels in the Fas-sensitive HD cell line HDLM2. We conclude that CD40L can act as an important anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells of HD and may be partly responsible for their survival 'in-vivo'.

Apoptosis↗

Requirement of the Lec35 gene for all known classes of monosaccharide-P-dolichol-dependent glycosyltransferase reactions in mammals.

The Lec35 gene product (Lec35p) is required for utilization of the mannose donor mannose-P-dolichol (MPD) in synthesis of both lipid-linked oligosaccharides (LLOs) and glycosylphosphatidylinositols, which are important for functions such as protein folding and membrane anchoring, respectively. The hamster Lec35 gene is shown to encode the previously identified cDNA SL15, which corrects the Lec35 mutant phenotype and predicts a novel endoplasmic reticulum membrane protein. The mutant hamster alleles Lec35.1 and Lec35.2 are characterized, and the human Lec35 gene (mannose-P-dolichol utilization defect 1) was mapped to 17p12-13. To determine whether Lec35p was required only for MPD-dependent mannosylation of LLO and glycosylphosphatidylinositol intermediates, two additional lipid-mediated reactions were investigated: MPD-dependent C-mannosylation of tryptophanyl residues, and glucose-P-dolichol (GPD)-dependent glucosylation of LLO. Both were found to require Lec35p. In addition, the SL15-encoded protein was selective for MPD compared with GPD, suggesting that an additional GPD-selective Lec35 gene product remains to be identified. The predicted amino acid sequence of Lec35p does not suggest an obvious function or mechanism. By testing the water-soluble MPD analog mannose-beta-1-P-citronellol in an in vitro system in which the MPD utilization defect was preserved by permeabilization with streptolysin-O, it was determined that Lec35p is not directly required for the enzymatic transfer of mannose from the donor to the acceptor substrate. These results show that Lec35p has an essential role for all known classes of monosaccharide-P-dolichol-dependent reactions in mammals. The in vitro data suggest that Lec35p controls an aspect of MPD orientation in the endoplasmic reticulum membrane that is crucial for its activity as a donor substrate.

Acyclic Monoterpenes↗

Ceramide-induced apoptosis in fas-resistant Hodgkin's disease cell lines is caspase independent.

We investigated whether cell-permeable, synthetic ceramide (C6 ceramide) could induce apoptosis in Fas-resistant Hodgkin's disease (HD)-derived cell lines. Despite strongly expressing the Fas-receptor, two of three HD-derived cell lines were resistant to Fas-mediated apoptosis. This resistance to Fas could not be attributed to differential Fas isoform generation patterns between the Fas-resistant and the Fas-sensitive cell lines. The Fas-resistant cell lines did not demonstrate the presence of Fas exon 8 deletion. Bcl-2 and BclxL levels were comparable between the Fas-resistant and the Fas-sensitive cell lines. C6 ceramide could induce apoptosis in both Fas-resistant cell lines and this was associated with a decrease in BclxL level. Caspase-1, caspase-3, or pan-caspase inhibitors could not prevent ceramide-induced apoptosis. Furthur, ceramide treatment did not lead to cleavage of caspase 3 or poly(ADP-ribose) polymerase, but caused a loss in mitochondrial transmembrane potential which could not be prevented by caspase inhibitors. Thus, we conclude that ceramide-induced apoptosis in Fas-resistant HD cell lines is caspase independent.

Amino Acid Chloromethyl Ketones↗

Granular acute lymphoblastic leukemia with hypereosinophilic syndrome.

A four-year-old boy presented with marked peripheral blood eosinophilia (absolute eosinophil count of 54 x 10(9)/1), features of hypereosinophilic syndrome, and acute lymphoblastic leukemia (ALL-L2), the latter characterized by the presence of granular blasts. Blasts were negative for myeloperoxidase, non-specific esterase, acid phosphatase, periodic-acid Schiff stain, and toluidine blue. They exhibited an early pre-B immunophenotype (TdT, CD19, CD10, CD20 and CD22 positive) and stained negative for T (CD7, CD2, CD5 and CD3) and myeloid markers (MPO, CD33 and CD13). Chromosomal analysis revealed a normal karyotype. To the best of our knowledge, this case represents the first report of the coexistence of granular ALL and hypereosinophilic syndrome.

Child, Preschool↗

Morphologic and imaging studies of duplicate optic canals in dry adult human skulls.

Three dry adult human skulls, two with bilateral and one with unilateral duplication of the optic canal were found. Their gross morphologic features were studied. Optic canals were separated by a septum of variable thickness dividing the posterior part of the canal into a large canal in the usual position and a smaller one inferior to it. The skull with unilateral duplication of the right side had a bony bar forming the carotico-clinoid canal. One of the skulls was disarticulated and its sphenoid had bilaterally duplicated optic canals divided by thin septa, both having a slit. Conventional radiography and CT scans for the optic canal were performed on two of these skulls but not on the disarticulated bone, and the imaging representations of these features were correlated with the anatomic findings on the dry skull.

Adult↗