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R Bansal

Publications and source records attributed to R Bansal.

At least 55 records · Page 3Linked to original sources
PubMed1997

FGF-2 converts mature oligodendrocytes to a novel phenotype.

Fibroblast growth factor (FGF)-2 differentially regulates oligodendrocyte progenitor proliferation and differentiation in culture, and modulates gene expression of its own receptors, in a developmental and receptor type-specific manner (Bansal et al., 1996a,b). Three FGF receptors (types 1, 2, 3) are expressed in postmitotic, terminally differentiating oligodendrocytes. Exposure of such cells to FGF-2 results in: (a) the down-regulation of myelin-specific gene expression (e.g., ceramide galactosyltransferase, 2',3'-cyclic nucleotide 3'-phosphohydrolase, myelin basic protein, proteolipid protein), (b) dramatic increases in the length of cellular processes in a time- and dose-dependent manner, (c) re-entrance into the cell cycle without accompanying mitosis, and (d) the alteration of the expression of both low- and high-affinity FGF receptors. Compared to oligodendrocyte progenitors, the differentiated oligodendrocytes treated with FGF-2 incorporate BrdU at a slower rates, exhibit different patterns of both FGF high- and low-affinity (syndecans) receptors, and are morphologically very different. In addition, they do not re-express the progenitor markers A2B5, NG2 or PDGFalpha receptor. Therefore, although the FGF-treated cells lose their differentiated OL/myelin markers, they do not revert to progenitors and clearly represent a different, apparently novel, phenotype both morphologically and biochemically, which we have termed NOLs. These data indicate that terminally differentiated oligodendrocytes retain the plasticity to reprogram their differentiation fate under the influence of environmental factors. The possible significance of this response to FGF relative to normal and pathological physiology is discussed. In particular, on the basis of these data we predict the appearance of cells in and around multiple sclerosis plaques with the phenotype O4+, NG2-, A2B5-, O1-, MBP-.

Animals↗
PubMed1997

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant.

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575-1450 g; gestational age: 26.8 weeks, range: 22-31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean +/- SEM) show that apparent volume of distribution (AVd) was 62.1 +/- 3.9 ml/kg, plasma t1/2 beta was 30.5 +/- 4.2 h, elimination rate constant (Kel) was 0.032 +/- 0.004 h-1, plasma clearance was 2.06 +/- 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 +/- 11.1 mg/l. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 +/- 54.5 mg/l and 113.6 +/- 58.2 mg/l, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 +/- 0.39%, n = 26) compared to adult plasma protein (mean +/- SE = 98.73 +/- 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.

Age Factors↗
PubMed1997

Distribution of mast cells in the axillary lymph nodes of breast cancer patients.

Fifty mastectomy specimens of carcinoma breast were studied for pattern of mast cell distribution in their axillary lymph nodes. When all axillary nodes were free of tumour, the mean mast cell count was 35.75/sq mm. In the metastatic node the mast cell count was inversely proportional to the amount of metastatic tumour. The mast cell number decreased (25.64/sq mm) as the metastasis developed in any of the enlarged axillary nodes. Their count diminished further (23.55/sq mm) as the amount of metastatic tumour increased in individual nodes and when tumour involved all enlarged nodes. Mean mast cell count was lowest (10.50/sq mm) in metaplastic carcinoma. The mast cells in metastatic nodes were found mainly at the edges of tumour deposits.

Axilla↗
PubMed1996

Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination, recognizes an antigen on the surface of oligodendrocytes.

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J mice chronically infected with Theiler's virus. To elucidate the mechanism of antibody-mediated remyelination, SCH94.03 was investigated by immunocytochemistry, flow cytometry, immunoelectron microscopy, Western blotting, and immuno-thin layer chromatography. All cell types investigated in vitro showed strong cytoplasmic staining with a pattern resembling a cytoskeletal protein. In contrast, among the primary cultured cells studied, only oligodendrocytes showed strong surface reactivity. Other cell types, including astrocytes, microglia, Schwann cells, myoblasts, and T and B lymphocytes, were negative. Mouse and rat oligodendrocytes which showed strong surface reactivity exhibited a well-differentiated morphology, and approximately 50% expressed myelin basic protein. Since oligodendrocyte progenitors were negative for surface staining, the expression of the antigens recognized by this monoclonal antibody appears to be developmentally regulated, i.e., transiently expressed on younger, terminally differentiating oligodendrocytes. Among the cell lines studied, only two rat oligodendrocyte lineage cell lines showed surface reactivity with SCH 94.03. Western blotting of secondary isolated oligodendrocytes lysates revealed reactivity with multiple protein bands of 27, 32, 50, 100, and 106 kDa, whereas there was no reactivity to lipid antigens by immuno-thin layer chromatography. These results raise the possibility that SCH94.03 recognizes a novel oligodendrocyte-specific surface antigen, and may act directly on oligodendrocytes to promote remyelination.

Animals↗
PubMed1996

Regulation of FGF receptors in the oligodendrocyte lineage.

Fibroblast growth factors (FGFs) affect a broad spectrum of developmentally regulated cellular responses involved in the control of growth and differentiation. To identify specific FGF receptor forms involved in these responses, we have characterized FGF receptor transcript expression, and its modulation by FGF-2, as enriched populations of oligodendrocyte progenitors differentiate into mature oligodendrocytes. The data demonstrate that the levels of mRNA expression for FGF high-affinity receptors-1, -2, and -3 are differentially regulated during lineage progression: FGF receptor-1 expression increases with lineage progression, FGF receptor-2 is predominantly expressed by terminally differentiated oligodendrocytes, and FGF receptor-3 reaches a peak level of expression in late progenitors and then declines upon further differentiation; FGF receptor-4 expression was not detected in oligodendrocytes. Distinct patterns of alternatively spliced variants of FGF receptor-1 and -2 transcripts are expressed: the predominant FGF receptor-1 transcripts contain three Ig-like domains (FGF receptor-1 alpha), whereas the FGF receptor-2 transcripts contain two Ig-like domains (FGF receptor-2 beta 2) and this form is up-regulated as oligodendrocytes differentiate. In addition, the expression of these receptors is differentially regulated by the ligand, FGF-2: FGF receptor-1 mRNA expression is up-regulated in early progenitors, and FGF receptor-2 mRNA expression is down-regulated in mature oligodendrocytes. Finally, astrocytes express FGF receptor-1, -2, and -3 transcripts, but at different levels and with different exon utilization (FGF receptor-1 beta, FGF receptor-2 beta 1/beta 2) compared to oligodendrocytes. To our knowledge this is the first report that demonstrates that the mRNA expression of these three FGF receptor types is differentially regulated in primary cells as they differentiate along a lineage from progenitors to terminally differentiated cells. We propose that this pattern of expression provides a molecular basis for the developmentally varying response of cells to a common ligand. For example, according to this hypothesis, in response to FGF-2, FGF receptor-1 transduces signals that stimulate the prolonged proliferation and migration of early progenitors, FGF receptor-3 promotes the proliferation and arrest of differentiation of late progenitors, and FGF receptor-2 transduces signals for terminal differentiation, but not proliferation, in mature oligodendrocytes.

Alternative Splicing↗
PubMed1996

Developmental and FGF-2-mediated regulation of syndecans (1-4) and glypican in oligodendrocytes.

Differentiating cells undergo developmentally regulated changes in cell-cell and cell-matrix adhesion that control migration through microenvironments, proliferation, and differentiation. The diversity of the patterns of expression of heparan sulfate proteoglycans (HSPGs), coupled with their interactions with extracellular matrix, cell adhesion molecules, and growth factors, has emphasized their critical importance in the regulation of these events. Syndecans (1-4), glypican, and cerebroglycan are membrane-associated HSPGs that have been implicated in these events in various tissues and several tumor cell lines. We have examined the developmental expression and FGF-2-mediated regulation of these HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, developmentally synchronized populations of OL-lineage cells at three stages of differentiation (early and late progenitors and mature OLs) showed that the expression of individual forms of these syndecans and glypican are developmentally regulated. Specifically, the level of expression of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to postmitotic mature cells. The expression of syndecan-1 and -3 had the inverse developmental pattern. Therefore, these two sets of molecules may have different roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progenitors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, and -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the levels of syndecan-2 and -4 and glypican were down-regulated. These results suggest that the individual syndecan molecules have distinct functions during the differentiation process and that multiple levels of regulation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.

Animals↗
PubMed1996

Brefeldin A inhibits the constitutive-like secretion of a sulfated protein in pancreatic acinar cells.

Sulfation is a common posttranslational modification of secretory proteins and serves as a valuable marker of constitutive and regulated secretory pathways. We investigated the cellular localization and the secretory behavior of sulfated macromolecules in the mouse pancreatic acinar cell. The major sulfated proteins of the cell were present in isolated zymogen granules, as determined by metabolic labeling with [35S]sulfate and subcellular fractionation. The sulfated proteins fell into three groups: gp300 is not secreted and is a component of the zymogen granule membrane; pancreatic lipase (56 kDa) and a 40 kDa protein are soluble and exhibit regulated secretion kinetics; and p82 is initially granule membrane associated, but is released from the cell with constitutive-like kinetics as a 75 kDa protein (p75). Secretion of p75 could be stimulated for up to 4 h after pulse labeling, presumably from immature secretory granules, but not after 6 h of chase. Treatment of cells with brefeldin A (BFA) at the start of the [35S]sulfate pulse resulted in almost total inhibition of sulfation. Addition of BFA during the chase (0-2 h) allowed normal basal and stimulated secretion of regulated secretory proteins, but reversibly inhibited the constitutive-like secretion of p75. In this case, the behavior of p75 was maintained as that of a regulated secretory protein for up to 6 h of chase. In untreated cells, immunofluorescence of p82/p75 was along the acinar lumen, and in small punctate structures in the apical cytoplasm. In BFA-treated cells, immunolabeling of p82/p75 was lost from the acinar lumen, and cytoplasmic labeling was finer and appeared to be associated with the secretory granule membranes. These data suggest a role for brefeldin A-sensitive coat formation in maturation of secretory granules after they bud from the TGN.

Amino Acid Sequence↗
PubMed1995

Cortisol status in different types of leprosy.

Basal plasma cortisol levels in 12 controls and 60 patients with different types of leprosy were within normal limits. They were significantly lower in multibacillary leprosy patients; this abnormality might be due to long standing stress leading to adrenal exhaustion. The plasma cortisol level significantly increased after the ACTH (Synacthen) stimulation test in all of the varieties of leprosy tested, which suggests that the adrenal reserve is maintained in such cases.

Adrenocorticotropic Hormone↗
PubMed1995

Early development and dispersal of oligodendrocyte precursors in the embryonic chick spinal cord.

Oligodendrocytes, the myelinating cells of the vertebrate CNS, originally develop from cells of the neuroepithelium. Recent studies suggest that spinal cord oligodendrocyte precursors are initially localized in the region of the ventral ventricular zone and subsequently disperse throughout the spinal cord. The characteristics of these early oligodendrocyte precursors and their subsequent migration has been difficult to assay directly in the rodent spinal cord due to a lack of appropriate reagents. In the developing chick spinal cord, we show that oligodendrocyte precursors can be specifically identified by labeling with O4 monoclonal antibody. In contrast to rodent oligodendrocyte precursors, which express O4 immunoreactivity only during the later stages of maturation, in the chick O4 immunoreactivity appears very early and its expression is retained through cellular maturation. In embryos older than stage 35, O4+ cells represent the most immature, self-renewing, cells of the chick spinal cord oligodendrocyte lineage. In the intact chick spinal cord, the earliest O4+ cells are located at the ventral ventricular zone where they actually contribute to the ventricular lining of the central canal. The subsequent migration of O4+ cells into the dorsal region of the spinal cord temporally correlates with the capacity of isolated dorsal spinal cord to generate oligodendrocytes in vitro. Biochemical analysis suggests O4 labels a POA-like antigen on the surface of chick spinal cord oligodendrocyte precursors. These studies provide direct evidence for the ventral ventricular origin of spinal cord oligodendrocytes, and suggest that this focal source of oligodendrocytes is a general characteristic of vertebrate development.

Animals↗
PubMed1995

Interns as health educators.

Interns are being used in two experimental health education projects in a rural area of India. In one the interns talk to mothers waiting with their children at an immunization clinic; in the other they train volunteer schoolchildren to act as school health guides in a child-to-child programme.

Child↗
PubMed1994

Regulation of gene expression in mature oligodendrocytes by the specialized myelin-like membrane environment: antibody perturbation in culture with the monoclonal antibody R-mAb.

We have previously shown that the growth of oligodendrocyte progenitors in the presence of a monoclonal antibody (R-mAb) reacting with a cell surface component reversibly blocks their further differentiation at a specific, late progenitor stage of the lineage. This block is characterized by a nearly complete elimination of the onset of terminal differentiation at the level of RNA expression. In the present study, mature oligodendrocytes already expressing markers of terminal differentiation were exposed to R-mAb. This resulted in a retraction of cell processes and the formation of round, swollen cells, and a dose-dependent, antibody-specific partial reduction (30-50%) in the steady state levels of markers of terminal differentiation. Upon removing the perturbing antibody, all markers returned to control levels within 2 days. This inhibition was due to modulations of the levels of the specific mRNAs and proteins, not to cell loss. Total protein and levels of a marker of astrocytic differentiation were not affected by the treatment. Monoclonal antibody O1 did not cause the effects observed with R-mAb. We conclude that the response of terminally differentiating oligodendrocytes to the effects of R-mAb is different from that of oligodendrocyte late progenitors. Whereas the latter appears to operate through perturbation of the onset of gene expression (mRNA transcription and/or stability), the partial down-regulation of previously activated myelinogenic gene expression appears to be due to the loss of a normal, myelin-like, membrane environment needed for the stability of myelin mRNA and protein components.

Animals↗
PubMed1994

Inhibition of protein and lipid sulfation in oligodendrocytes blocks biological responses to FGF-2 and retards cytoarchitectural maturation, but not developmental lineage progression.

We have examined the interfaces between protein and lipid sulfation, the response of progenitor cells to specific growth factors, and developmental lineage progression. The experimental system used is the oligodendrocyte (OL), the cell responsible for myelination of axons in the central nervous system. The ability to regulate the growth and differentiation of oligodendrocytes in primary cultures growing in defined medium offers a particularly attractive model for these interrelated areas of cell and developmental biology. Sulfation was inhibited in this system by growing cells in sodium chlorate, a competitive inhibitor of sulfation. Four principal conclusions are drawn from the data. First, heparan sulfate proteoglycan is a necessary cofactor for the environmental regulation by FGF-2 of nontransformed oligodendrocyte progenitors, including both the mitogenic response and the inhibition of terminal differentiation at a specific stage of the lineage. Second, the differentiation of oligodendrocyte progenitors from an early to a mature stage can occur in the absence of sulfation. Third, however, the formation of cellular processes and myelin-like sheets is retarded, leading to the prediction that sulfated molecules are critically involved in aspects of oligodendrocyte differentiation directly relating to myelination per se. Fourth, the developmental proligodendroblast antigen, POA, is a sulfated molecule. The results provide clear evidence for the importance of sulfation for the responses of OL progenitors to FGF-2 and for OL cytoarchitectural maturation, while demonstrating an ability of OL progenitors to undergo lineage progression in its absence.

Animals↗