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Biomedical subjects

A Samanta

Publications and source records attributed to A Samanta.

At least 19 recordsLinked to original sources
PubMed2000

Aberrant processing of oxidative DNA damage in systemic lupus erythematosus.

Defective DNA damage processing has been reported in systemic lupus erythematosus (SLE). Vitamin C may modulate formation/removal of the oxidative DNA lesion 8-oxo-2'-deoxyguanosine (8-oxodG). Baseline levels of 8-oxodG measured in SLE serum, urine and PBMC DNA did not differ significantly from healthy subjects. In contrast to healthy subjects, no significant decrease in PBMC 8-oxodG or increase in urinary 8-oxodG was noted in vitamin C supplemented SLE patients. A significant, although attenuated, increase in serum 8-oxodG was detected in SLE patients, compared to healthy subjects. These data support putative abnormalities in the repair/processing of 8-oxodG in SLE.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Evaluation of ambulatory performance of the arm propelled three-wheeled chair using heart rate as a control index.

PURPOSE: The Arm propelled three wheeled chair (APTWC) is in common use in the economically poor countries for outdoor ambulation, the propulsion force of which is exerted by arm cranking in asynchronous fashion. The purpose of the study was to assess the ambulatory performance of the users of the device using heart rate as a control index, at graded speeds. METHOD: Fifteen regular users of APTWC male with paraplegia and poliomyelitis were ambulated at seven different graded speeds in outdoor settings and the resting and ambulatory heart rate was measured during steady state and then physiological cost index and comfortable speed of propulsion was computed. RESULTS: The physiological strain, linear regression of the relationship between heart rate and speed with correlation coefficient of r = 0.86 (p < 0.001), polynomial regression of the relationship between physiological cost index (PCI) and speed with correlation coefficient of r = 0.83 (p < 0.001) and comfortable speed of propulsion (120 m/min) was reported. CONCLUSIONS: Heart rate can be used to evaluate the ambulatory performance of the device, quantifying energy economy for outcome evaluation and decision making for clinical recommendation.

Adult↗
PubMed2000

Modification of biophysical properties of lung epithelial Na(+) channels by dexamethasone.

There is considerable interest in identifying the basic mechanisms by which dexamethasone alters ion transport across the adult alveolar epithelium. Herein, we incubated synchronized A549 cells, a human alveolar epithelial cell line, with dexamethasone (1 microM) for 24-48 h. When normalized to HPRT (a housekeeping gene), A549 beta- and gamma-subunit mRNA levels for the human amiloride-sensitive epithelial sodium channel (hENaC), assessed by RT-PCR, increased by 1.6- and 17-fold respectively, compared with control values (P < 0.05). These changes were abolished by actinomycin D, indicating transcriptional regulation. Western blotting studies revealed that dexamethasone also increased expression of beta- and gamma-hENaC protein levels. In contrast, alpha-hENaC mRNA increased by onefold (P > 0.05) and alpha-hENaC protein level was unchanged. Incubation of A549 cells with dexamethasone increased their whole cell amiloride-sensitive sodium currents twofold and decreased the K(0.5) for amiloride from 833 +/- 69 to 22 +/- 5.4 nM (mean +/- SE; P < 0.01). Single channel recordings in the cell-attached mode showed that dexamethasone treatment increased single channel open time and open probability threefold and decreased channel conductance from 8.63 +/- 0.036 to 4. 4 +/- 0.027 pS (mean +/- SE; P < 0.01). We concluded that dexamethasone modulates the amiloride-sensitive Na(+) channels by differentially regulating the expression of beta- and gamma-subunits at the mRNA and protein levels in the human A549 cell line, with little effect on alpha-hENaC subunit.

Administration, Topical↗
PubMed2000

Biophysical properties and molecular characterization of amiloride-sensitive sodium channels in A549 cells.

Amiloride-sensitive Na(+) channels, present in fetal and adult alveolar epithelial type II (ATII) cells, play a critical role in the reabsorption of fetal fluid shortly after birth and in limiting the extent of alveolar edema across the adult lung. Because of the difficulty in isolating and culturing ATII cells, there is considerable interest in characterizing the properties of ion channels and their response to injury of ATII cell-like cell lines such as A549 that derive from a human alveolar cell carcinoma. A549 cells were shown to contain alpha-, beta-, and gamma-epithelial Na(+) channel mRNAs. In the whole cell mode of the patch-clamp technique (bath, 145 mM Na(+); pipette, 145 mM K(+)), A549 cells exhibited inward Na(+) currents reversibly inhibited by amiloride, with an inhibition constant of 0.83 microM. Ion substitution studies showed that these channels were moderately selective for Na(+) (Na(+)-to-K(+) permeability ratio = 6:1). Inward Na(+) currents were activated by forskolin (10 microM) and inhibited by nitric oxide (300 nM) and cGMP. Recordings in cell-attached mode revealed the presence of an amiloride-sensitive Na(+) channel with a unitary conductance of 8.6 +/- 0.04 (SE) pS. Channel activity was increased by forskolin and decreased by nitric oxide and the cGMP analog 8-bromo-cGMP. These data demonstrate that A549 cells contain amiloride-sensitive Na(+) channels with biophysical properties similar to those of ATII cells.

Amiloride↗
PubMed1998

Development of amphotericin B loaded nanoparticles.

Amphotericin B loaded nanoparticles were successfully prepared by in-situ emulsion polymerization technique using Ethylcyanoacrylate monomer. Scanning Electron Micrographs (SEM) of the nanoparticles showed that the particles were spherical and discrete. Average particle size analysis of two samples were found to be within the range of 475.3 +/- 91.68 to 479.75 +/- 105.49 nm. Thus the particles formed were within the colloidal range. With increase in monomer concentration, the percentages of drug adsorbed on the surface of nanoparticles were also increased. At the optimum concentration of Ethylcyanoacrylate (21.6 microliters/ml), 72.1% of Amphotericin B was adsorbed.

Amphotericin B↗
PubMed1996

Mapping air contaminants indoors using a prototype computed tomography system.

Single and multiple plumes of sulphur hexafluoride were measured and mapped using a prototype open-path Fourier transform infrared spectrometer (OP-FTIR)-computed tomography (CT) system in an indoor exposure chamber. The OP-FTIR-CT system accurately mapped the position of concentration peaks at different locations in the chamber, and estimated concentrations within a range of 4-50% when compared with point samples measured by gas chromatography with an electron capture detector. Two OP-FTIR spectrometer ray configurations, one with 100 rays and the other with 136 rays, were used to scan the chamber and reconstruct the concentration maps. Ray configuration and time to scan the entire chamber were found to have a profound effect on the quality of the reconstructed maps. The ability to obtain real-time, non-invasive measurements, and to generate spatially and temporally resolved maps of multiple chemicals, makes the OP-FTIR-CT system a promising technique for monitoring source emissions and evaluating exposures to air contaminants in a workplace.

Air Pollutants↗
PubMed1995

Identification of a 140 kDa protein of rat presynaptic terminal membranes encompassing the active zones.

A polyclonal antiserum raised against the carboxy-terminal 17 amino acids of the rat p185c-neu (anct) reacted with a 140 kDa polypeptide in membranes of synaptosome fractions from neocortex and hippocampus of 11-day-old and adult rats. The same antiserum reacted with a 185 kDa polypeptide in microsome membranes from rat pheochromocytoma cells (PC12). By light microscopic immunocytochemistry, the anct antibodies against the 140 kDa protein were localized in the neuropile of brain, cerebellum and spinal cord of 11-day-old and adult rats. Especially prominent staining was obtained in the CA2-CA3 zones of the hippocampus, and in the substantia gelatinosa in the spinal cord. The finely granular and diffuse pattern of the immunostain was consistent with synaptic localizations. Interestingly, antibodies against the entire endodomain of p185c-neu (a-Bacneu) were localized in granular structures, probably representing axo-somatic and axo-dendritic synapses, on a subset of pyramidal neurons of the CA3 zone. By immunoelectron terminals in the giant mossy fiber type in the CA3 and CA4 regions. The immunolocalization of the anct antibodies was restricted in segments of the presynaptic membrane facing the synaptic cleft which include the active zone. The identify and function of the 140 kDa membrane protein of rat brain presynaptic terminals, detected by the anct antibodies, is unknown. The 140 kDa protein may be related to p185c-neu, a tyrosine kinase, or to other known or unknown kinases.

Amino Acid Sequence↗
PubMed1995

A kinase associated with chromatin that can be activated by ligand-p185c-Neu or epidermal growth factor-receptor interactions.

Some growth factors transduce positive growth signals, while others can act as growth inhibitors. Nuclear signaling events of previously quiescent cells stimulated with various growth factors have been studied by isolating the complexed chromatin-associated proteins and chromatin-associated proteins. Signals from the plasma membrane are integrated within the cells and quickly transduced to the nucleus. It is clear that several growth factors, such as epidermal growth factor, transforming growth factor alpha (but not transforming growth factor beta), and platelet-derived growth factor, utilize similar intracellular signaling biochemistries to modulate nucleosomal characteristics. The very rapid and consistent phosphorylation of nuclear p33, p54, and low molecular mass proteins in the range of 15-18 kDa after growth factor stimulation implies that there is a coordination and integration of the cellular signaling processes. Additionally, phosphorylation of p33 and some low molecular mass histones has been found to occur within 5 min of growth factor treatment and to reach a maximum by 30 min. In this study, we report that Neu receptor activating factor also utilizes the same signaling mechanism and causes p33 to become phosphorylated. In addition, both the tumor promoter okadaic acid (which inhibits protein phosphatases 1 and 2A) and phorbol ester (phorbol 12-tetradecanoate 13-acetate) stimulate phosphorylation of p33, p54, and low molecular mass histones. However, transforming growth factor beta, which is a growth inhibitor for fibroblasts, fails to increase p33 phosphorylation. In general, p33 phosphorylation patterns correspond to positive and negative mitogenic signal transduction. p33 isolated from the complexed chromatin-associated protein fraction appears to be a kinase, or tightly associated with a kinase, and shares antigenicity with the cell division cycle-dependent Cdk2 kinase as determined by antibody-dependent analysis. The rapid phosphorylation of nucleosomal proteins may influence sets of early genes needed for the induction and progression of the cell cycle.

Animals↗
PubMed1995

Prevention of breast tumour development in vivo by downregulation of the p185neu receptor.

Certain strains of transgenic mice that express the rat neu oncogene (neuT) in mammary epithelial cells develop breast tumours at an average of 44 weeks of age. In this study, intraperitoneal injection of a monoclonal anti-receptor antibody specific for the rat neuT oncogene product dramatically affected tumour development in these transgenic mice in a dose-dependent manner. A significant proportion (50%) of mice, when injected with anti-receptor antibodies, did not develop tumours even after 90 weeks of age. The phosphotyrosine levels of the membrane fraction of breast tissues in the anti-receptor antibody-treated mice were almost completely abolished when a higher dose of antibodies was used. This study demonstrates, for the first time, that immunologic manipulation of an oncogene product can effectively prevent the development of tumours in a rodent transgenic model.

Animals↗
PubMed1995

Unexpected transcriptional signals in normal and mitotically defective cells mediated through cytokine and growth factor receptors.

Polypeptide growth factors and cytokines mediate their biochemical functions through their responsive receptors. Known cytokine receptors do not possess intrinsic kinase domains whereas several polypeptide growth factor receptors do. Nevertheless, both classes of ligands are capable of activating sets of overlapping genes. In human epidermoid carcinoma cells, for example, both cytokines and epidermal growth factor (EGF) promote a common transcriptional activation signal through the tyrosine phosphorylation of stat91 (signal transducer and activator of transcription) proteins. The stat family of cytoplasmic proteins also appear to have dual functions. Tyrosine phosphorylated 'stats' are employed for signal transduction and, second, for activation of transcription of several genes. The transcription factor-SIE-DNA binding patterns are now known to be different for EGF and interferon-gamma IFN-gamma-treated cells. Nevertheless, in the active DNA-bound complex, the stat91 polypeptide is a component found in either EGF or INF-gamma-treated extracts. Other stat family members of transcription factors may also be present in the complexes. In this case, tyrosine phosphorylated stat91 polypeptides may form into homodimeric or heterodimeric assemblies with other stat-related transcription factors. We describe a novel stat-related factor, p93, that is found in EGF-treated A431 cell extracts but appears to be absent in bovine fibroblast growth factor (bFGF), IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), and untreated cells. p93 appears to be antigenically related to stat91. p185c-neu+, EGFr+ (M1), and p185c-neu- kinase inactive, EGFr+ (NEN757) expressing cells undergo different mitotic responses to EGF. M1 can respond to EGF mitotically while NEN757 cannot. Both cell lines respond to 10 ng/ml of EGF and also to IFN-gamma in transducing transcriptional activation signals to the nucleus, despite the distinct growth response to EGF. Our work has analyzed the stat pathway in these types of cells and found similar patterns of usage despite the distinct EGF-responsive features. Cytoplasmic nonreceptor tyrosine kinases Jak1 and Jak2 may be involved in the activation of stat91 and other transcription factors in EGF and IFN-gamma signaling pathways. Collectively, these studies suggest that the major EGF-stimulated mitotic growth pathways may not be absolutely linked to the stat91 signaling pathways and that such transcription complexes are more complex than previously reported.

Animals↗
PubMed1994

Ligand and p185c-neu density govern receptor interactions and tyrosine kinase activation.

The neu protooncogene (also known as c-erbB2, NGL, and HER2) encodes a 185-kDa transmembrane glycoprotein with intrinsic tyrosine kinase activity that resembles the receptor for epidermal growth factor. The p185 gene and protein were originally identified in the brain and are thought to play a critical role in neurogenesis. Aberrant c-erbB2 protein overexpression also occurs in several human adenocarcinomas. A ligand for p185, neu-activating factor (NAF), specifically binds to neu receptor and increases the p185c-neu tyrosine phosphorylation in vitro and in vivo in a dose-dependent manner. We now show that NAF specifically binds to purified p185 expressed in baculovirus. Direct binding analysis showed that NAF binds with high affinity (Kd = 1.3 nM). We have investigated changes in the structure and association state of baculovirus-produced neu holoreceptor that are induced by ligand binding. In this study, we used sucrose gradients to show that purified p185c-neu exists mainly in the monomeric form at low concentrations, whereas at higher concentrations p185c-neu exists as dimers or multimers. At low concentrations, but in the presence of ligand, p185c-neu sediments as a dimeric or multimeric form. Monomer-oligomer interconversion is absolutely ligand dependent at low receptor concentrations. The high molecular weight form of the receptor is enzymatically more active, as a consequence of ligand-driven activation of the receptor kinase. Oncogenic p185neu receptors sediment predominantly as high molecular weight forms and have constitutively active kinases.

Animals↗
PubMed1994

Aerobic capacity of the brick-field workers in eastern India.

Forty two male brick-field workers of two age groups, viz. 20-29 and 30-39 yrs were studied with a view to determine their aerobic capacity (VO2 max). The average values of VO2 max in l.min-1 showed only small change between the young and the aged groups, but the values of the VO2 max in ml.kg.-1min-1 showed significant difference between the groups due to body weight increase in the aged group. The aerobic capacity of the workers engaged in heavy manual work such as puddlers and load carriers were found to be comparatively higher and a positive significant relationship has been established between the aerobic capacity and different occupations in the brick-field workers.

Adult↗
PubMed1994

The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies.

A variety of pathways exist to transmit biological signals. One mechanism used for the regulated control of cell growth and differentiation is through the transduction of signals resulting from the binding of soluble polypeptide growth factors to their cognate receptors. The specificity of growth factor action is mediated by the interaction of ligand with cognate receptors which can lead to exquisite control in a tissue- and developmental-specific manner. In addition, individual receptors on the cell surface can form complex assemblies with other receptor/signal transduction molecules that potentially lead to additional levels of signal transmissions. Biological signaling by peptide ligands can be mediated through the enzymatic activation of the receptor resulting in the triggering of a defined biochemical pathway. Ultimately, a mitogenic or differentiation signal is delivered to the nucleus, completing the biological action of the growth factor. The biochemical mechanisms of signal transduction by the p185 neu/c-erbB-2 growth factor receptor and the subsequent physiological responses are the topics of this review. Study of the p185 growth factor receptor has helped to illustrate the functional role of receptor homo- (and hetero-) dimerization in enzyme activation and, in malignant cells, the detrimental results of structural mutations or aberrant gene expression which may effect this dimerization. The ability of one type of growth factor receptor to affect the activity of another (as illustrated by the p185/epidermal growth factor receptor heterodimeric complex) is likely to be a common regulatory feature of growth factor receptor action. The nomenclature to be used in this review will refer to the oncogenic mutated form of the rat protein as 'p185neu', the proto-oncogenic rat protein as 'p185c-neu' and the human form as 'p185c-erbB-2'. The term 'p185' will be used to refer to any type of protein, regardless of the source.

Animals↗
PubMed1993

Is osteoarthritis in women affected by hormonal changes or smoking?

The influence of sex hormone related events and smoking on the development of OA in women was investigated in a case-controlled postal survey. One hundred and twenty-nine patients with nodal generalized osteoarthritis (NGOA) and 145 with non-nodal pauciarticular large joint osteoarthritis (LJOA) were identified from the database of a Nottingham OA clinic. For each patient, three age-matched controls were randomly selected from the same general practice. Sixty-three per cent of questionnaires (690/1096) were returned: NGOA, 95; NGOA controls, 226; LJOA, 113; LJOA controls, 256. There were no differences in age at menarche or menopause, rates of hysterectomy, oral contraceptive use, or hormone replacement use between cases and controls. Fewer OA patients had ever smoked [(Odds Ratio (OR) 0.65, 95% Confidence Interval (CI) 0.45-0.95)] and subset analysis demonstrated that this negative association occurred only in the LJOA group (OR 0.43, CI 0.25-0.72), particularly in those with knee OA (OR 0.29, CI 0.14-0.62). A previous successful pregnancy was negatively associated with NGOA (OR 0.47, CI 0.24-0.95). This study demonstrates no association between oestrogen-related hormonal events and OA, but a negative association between smoking and LJOA. Such data supports the concept that OA is a heterogeneous disease and underlines the need to differentiate OA subsets.

Age Factors↗