Biased usage of variable and constant-region Ig genes by IgG+, CD5+ human leukemic B cells.
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Antigens, CD↗
Biomedical subjects
J Silver
Publications and source records attributed to J Silver.
Chondroitin sulfate as a regulator of neuronal patterning in the retina.
Highly sulfated proteoglycans are correlated with axon boundaries in the developing central nervous system which suggests that these molecules affect neural pattern formation. In the developing mammalian retina, gradual regression of chondroitin sulfate may help control the onset of ganglion cell differentiation and initial direction of their axons. Changes induced by the removal of chondroitin sulfate from intact retinas in culture confirm the function of chondroitin sulfate in retinal histogenesis.
Animals↗
Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat.
High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
Actins↗
Changes in both gp120 and gp41 can account for increased growth potential and expanded host range of human immunodeficiency virus type 1.
Virus derived from an infectious molecular clone of the ELI strain of human immunodeficiency virus type 1 (HIV-1) replicates well in peripheral blood mononuclear cells and in some CD4-positive cell lines but exhibits a delayed time course of infection in CEM and H9 cells and fails to infect SupT1 and U937 cells. If the virus that emerges from infected H9 cells is used to infect CEM and H9 cells, the time course of infection is accelerated and the virus is able to infect U937 and SupT1 cells. In this study, we used the technique of polymerase chain reaction-single-strand conformation polymorphism to localize changes in both the extracellular gp120 and the transmembrane gp41 components of the envelope gene associated with adaptation to growth in tissue culture cell lines. Specifically, mutations were identified both in a region of gp120 implicated in CD4 binding and in the amino-terminal portion of gp41 adjacent to the region involved in fusion. No changes were found in the V3 loop of gp120, a region previously shown to be involved in viral tropism. When these mutations were introduced into the original molecular clone, they conferred an enhanced replicative capacity on ELI. These results demonstrate that two additional determinants in the HIV-1 envelope protein influence viral tropism and growth in vitro. They also may have important implications for the generation of viruses with increased growth potential and expanded host range seen in the late stages of HIV disease.
Amino Acid Sequence↗
Estrogen receptors and biologic response in rat parathyroid tissue and C cells.
The expression of the PTH and calcitonin genes is dramatically decreased by 1,25(OH)2D3 in vivo, and the PTH gene expression is increased by hypocalcemia. We have now studied the effect of estrogens on the expression of these genes in vivo. 17 beta-Estradiol, given to ovariectomized rats, led to a fourfold increase in PTH mRNA and calcitonin mRNA levels. These effects occurred 24 h after single injections of 37-145 nmol estradiol, or after constant infusions of 12 pmol/d for 1 or 2 wk, where there was no effect on serum calcium levels. The estrogen receptor mRNA was demonstrated in the thyroparathyroid tissue by polymerase chain reaction. The estrogen binding was localized to the parathyroid and C cells by immunohistochemistry. Uterus weight was increased by repeated larger doses (73 nmol/d x 7) of estradiol, but not by the small doses (12 pmol/d for 1 or 2 wk) which were effective on the PTH and calcitonin genes, suggesting a sensitive endocrine effect. These results confirm that the parathyroid and C cells are target organs for estrogen, leading to an increased expression of PTH and calcitonin, which by their combined anabolic effect on bone would help prevent osteoporosis.
Animals↗
Complications of intrathecal baclofen delivery.
The medical records of 46 consecutive patients who have had intrathecal Baclofen drug delivery systems implanted in the National Spinal Injuries Centre, the Paddocks Hospital Spinal Unit, Princes Risborough, Lodge Moor Hospital Spinal Unit, Sheffield, the Northern Regional Spinal Injuries Unit, Hexham and The Radcliffe Infirmary, Oxford, were reviewed. Patients were contacted to describe their views on the treatment. The complications of the treatment are described. Some, such as overdose and meningitis are particularly hazardous. Others, in particular pump tubing revisions, are more of an inconvenience and time consuming for the patient and physician. If the serious risks of this valuable treatment are to be minimized and the therapy applied most effectively than a well co-ordinated team is essential, involving in particular the physician responsible for the initial assessment and follow-up of the patient and an experienced surgeon. It is recommended that only a small number of centres in the UK undertake these implants.
Adolescent↗
Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms.
By isolating genomic DNA clones that encompass the mouse Cyl-1 (cyclin D1) locus, we have identified a putative CpG island close to the 5' end of the gene. Pulsed-field gel electrophoresis with probes derived from either the 5' or 3' side of the CpG island established physical linkage to two independent markers on mouse chromosome 7, in a region that is syntenic with human chromosome 11q13. On the 3' side, Cyl-1 is approximately 75 kb from Hst-1 and Int-2, although there is an additional CpG island in the intervening DNA, while on the 5' side, Cyl-1 is less than 300 kb from Fis-1, an integration site for Friend murine leukaemia virus. As there is no intervening CpG island, proviral insertions at Fis-1 could influence the expression of Cyl-1 and we describe two virally induced tumours in which this appears to be the case. The data suggest that proviral insertions near Cyl-1 in mouse lymphomas are functionally equivalent to the BCL1 translocations that activate cyclin D1 expression in human B-cell malignancies.
Animals↗
Friend murine leukaemia virus is integrated at a common site in most primary spleen tumours of erythroleukaemic animals.
A common proviral integration site was identified and characterized in erythroleukaemias induced by Friend murine leukaemia virus (F-MuLV). Using inverse polymerase chain reaction, we found a proviral integration site common to at least 90% of 20 primary tumours tested. This site was identical to Fli-1, a locus recently reported by others to be rearranged in 75% (9/12) of cell lines established from spleens of erythroleukaemic mice and to code for a member of the ets gene family. Our data suggest that about half of the F-MuLV-induced erythroleukaemias contained more than one cell clone with a proviral integration in Fli-1, with different individual integration sites within Fli-1 in each cell clone. All proviruses were found to be integrated in the same transcriptional orientation with respect to flanking cellular DNA. We discuss these findings in relation to multistage models of neoplasm.
Animals↗
T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type.
We compared T cell receptor (TCR) V-segment frequencies in human leukocyte antigen (HLA) identical siblings to sibling pairs who differ at one or both HLA haplotypes using four V beta-specific and one V alpha-specific monoclonal antibody. In every one of nine families HLA-identical sibs had the most similar patterns of V-segment frequencies in their peripheral blood, whereas totally mismatched sibs were, in general, the most dissimilar; HLA haploidentical sibs tended to be intermediate between the two groups. The degree of similarity among HLA-identical sibs was comparable to that observed among three pairs of identical twins suggesting that HLA is the major genetic component influencing TCR V-segment frequency. Consistent with this observation, it was found that the frequency of T cells expressing particular V beta segments was skewed towards either CD4+ or CD8+ cells indicating that T cells expressing some V beta genes may be positively selected primarily by class I or class II major histocompatibility complex proteins. Finally, it was observed that individuals who express the HLA class I specificity, B38, tend to express high levels of V alpha 2.3+ cells among their CD8+ T cells. These observations represent definitive proof that human V-segment frequencies are profoundly influenced by the HLA complex.
Alleles↗
Formation of the retinal ganglion cell and optic fiber layers.
The early development of retinal ganglion cell and the optic fiber layers has been studied by examining the morphology of differentiating retinal ganglion cells using immunoelectron microscopy and a monoclonal antibody against neuron-specific beta-tubulin. This antibody identified retinal ganglion cells during the stages of their most active differentiation and axonogenesis prior to maturation of other retinal neurons. The changing morphology of retinal ganglion cells during these early stages is consistent with a differentiation sequence in which axonogenesis and translocation of the cell body to the vitreal surface occur while the cell is still attached to the vitreal margin through its vitreal endfeet. Thus, the mechanism of retinal ganglion cell axon generation and soma migration to the vitreal surface appears to involve maintenance of this attachment which may act as both a focus for axon differentiation and an anchor for directed nuclear translocation to the vitreal margin.
Animals↗
Electrical properties of axons within probst bundles of acallosal mice and callosi that have reformed upon glial-coated polymer implants.
Lesioning of the developing cerebral midline and corpus callosum of mice results in the formation of bilateral masses of axons known as Probst's longitudinal bundles. These ectopic axons were examined using an in vitro brain slice technique, and they were found to be functional and to have electrical properties that were similar to those of the unlesioned corpus callosum at a comparable age. When a nitrocellulose bridge is properly oriented at the site of the callosal lesion in neonates, the implant will support the migration of glia which, in turn, promote the redirection of callosal axons across the midline. These axons were also analyzed by in vitro brain slice techniques, and they were found to be functional and to have electrical properties that were similar to the unlesioned corpus callosum with respect to conduction velocity and chronaxie but dissimilar with respect to charge threshold and rheobase current.
Animals↗
An atlas of the prenatal mouse brain: gestational day 14.
A prenatal atlas of the mouse brain is presently unavailable and is needed for studies of normal and abnormal development, using techniques including immunocytochemistry and in situ hybridization. This atlas will be especially useful for researchers studying transgenic and mutant mice. This collection of photomicrographs and corresponding drawings of Gestational Day (GD) 14 mouse brain sections is an excerpt from a larger atlas encompassing GD 12-18. In composing this atlas, available published studies on the developing rodent brain were consulted to aid in the detailed labeling of embryonic brain structures. C57Bl/6J mice were mated for 1 h, and the presence of a copulation plug was designated as GD 0. GD 14 embryos were perfused transcardially with 4% paraformaldehyde in 0.1 M phosphate buffer and embedded in paraffin. Serial sections (10 microns thickness) were cut through whole heads in sagittal and horizontal planes. They were stained with hematoxylin and eosin and photographed. Magnifications were 43X and 31X for the horizontal and sagittal sections, respectively. Photographs were traced and line drawings prepared using an Adobe Illustrator on a Macintosh computer.
Animals↗
A carbohydrate polymer that effectively prevents epidural fibrosis at laminectomy sites in the rat.
We demonstrate that a carbohydrate polymer, designated GL402, effectively inhibits epidural fibrosis in a rat laminectomy model. A total laminectomy in Lewis rats was performed at lumbar vertebrae 3 and 5. GL402 or phosphate buffer solutions in gelatin sponges were applied to the laminectomy sites. Epidural fibrosis was measured, using a double-blind protocol, 2 weeks postoperatively either by gross anatomical evaluation (blunt dissection) or by histological evaluation. Local application of GL402 produced nearly complete inhibition of epidural fibrosis, whereas extensive scar formation and bone growth occurred after local application of buffer or other purported anti-fibrotics. In laminectomy sites treated with GL402 the dura mater was essentially free of adhering fibrosis and bone growth was dramatically decreased. With reduction of postlaminectomy fibrosis, the spinal nerve roots are more mobile and therefore may be less prone to recurrent nerve root compression. The dramatic reduction of epidural fibrosis by GL402 will make reoperative disc surgery safer due to greater accessibility of the laminectomy site. This compound may be useful in preventing surgical adhesions in other sites as well.
Animals↗
HIV-associated nephropathy in transgenic mice expressing HIV-1 genes.
Transgenic mice were produced that bore copies of a defective HIV provirus. The transgenic offspring from three independently derived mouse lines manifested renal disease associated with proteinuria, a high mortality rate, and HIV-specific gene expression in the kidney. An early histopathological lesion in the kidney was focal glomerulosclerosis. Moribund animals had diffuse glomerulosclerosis with prominent microcystic tubular dilatation, tubular epithelial degeneration, and interstitial nephritis. Electron microscopy revealed ultrastructural features consistent with the glomerulosclerosis: effacement of the foot processes of visceral epithelium and an increase in mesangial cell matrix. Transgenic mice variably expressed 6-, 4.3-, and 2-kb HIV-specific RNAs and HIV-related polypeptides in several tissues including kidney. Immunocytostaining revealed the presence of HIV-related protein in the glomeruli of affected animals. Glomerulopathy in these transgenic mice and HIV-associated nephropathy in man have similar features.
Animals↗
The mouse homolog of the Gibbon ape leukemia virus receptor: genetic mapping and a possible receptor function in rodents.
The mouse homolog of the Gibbon ape leukemia virus (GALV) receptor (Glvr-1) was mapped to mouse Chromosome 2 (Chr 2) by Southern blot analysis of somatic cell hybrids and positioned on this chromosome using an interspecies genetic cross. Mouse Chr 2 also encodes a receptor (Rec-2) for the wild mouse virus M813. To investigate whether Glvr-1 and Rec-2 could be the same gene, we sought evidence for sequence homology between the env- genes of their respective viruses. Southern blot hybridization with GALV-derived env and pol-env probes failed to detect any homology between GALV and M813, but did show that all mouse species tested carry numerous copies of GALV-related sequences. We speculate that a functional receptor for GALV-related viruses was expressed during Mus evolution.
Animals↗
Glial cells. The unsung heroes of the brain. One company's view.
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Animals↗
A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth.
In the developing retina, retinal ganglion cell (RGC) axons elongate toward the optic fissure, even though no obvious directional restrictions exist. Previous studies indicate that axon-matrix interactions are important for retinal ganglion cell axon elongation, but the factors that direct elongation are unknown. Chondroitin sulfate proteoglycan (CS-PG), a component of the extracellular matrix, repels elongating dorsal root ganglion (DRG) axons in vitro and is present in vivo in the roof plate of the spinal cord, a structure that acts as a barrier to DRG axons during development. In this study, we examined whether CS-PG may regulate the pattern of retinal ganglion cell outgrowth in the developing retina. Immunocytochemical analysis showed that CS-PG was present in the innermost layers of the developing rat retina. The expression of CS-PG moved peripherally with retinal development, always remaining at the outer edge of the front of the developing axons. CS-PG was no longer detectable with immunocytochemical techniques when RGC axon elongation in the retina is complete. Results of studies in vitro showed that CS-PG, isolated from bovine nasal cartilage and chick limb, was inhibitory to elongating RGC axons and that RGC growth cones were more sensitive to CS-PG than were DRG neurites tested at the same concentrations of CS-PG. The behavior of retinal growth cones as they encounter CS-PG was characterized using time-lapse video microscopy. Filopodia of the RGC growth cones extended to and sampled the CS-PG repeatedly. With time, the growth cones turned to avoid outgrowth on the CS-PG and grew only on laminin. While numerous studies have shown the presence of positive factors within the retina that may guide developing RGC axons, this is the first demonstration of an inhibitory or repelling molecule in the retina that may regulate axon elongation. Taken together, these data suggest that the direction of RGC outgrowth in the retina may be regulated by the proper ratio of growth-promoting molecules, such as laminin, to growth-inhibiting molecules, like CS-PG, present in the correct pattern and concentrations along the retinal ganglion cell pathway.
Animals↗
Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes.
The extracellular matrix (ECM) molecules chondroitin-6-sulfate proteoglycan (CS-PG) and cytotactin/tenascin (CT), present on subpopulations of astroglia or their precursors during development, can inhibit neurite outgrowth in vitro. However, it is not known whether these molecules are expressed within the mature CNS following injury, where they could contribute to regenerative failure. Thus, the expression of various ECM molecules that affect axon growth was examined in areas of reactive gliosis caused by implanting a piece of nitrocellulose into the cortex of neonatal and adult animals. The expression of these molecules was compared to the amount of neurite outgrowth that occurred in vitro when the damaged CNS tissue from animals of various ages was removed intact and used as a substrate in explant culture. The results demonstrate that the growth-promoting molecules laminin, collagen type IV, and fibronectin were present around the implant in all experimental groups. In comparison, CS-PG and CT were present within and around the area of the lesion only in adult animals. In vivo, these molecules were colocalized with intensely glial fibrillary acidic protein (GFAP)-positive astrocytes in and immediately adjacent to the scar, but not with other equally intensely GFAP-positive astrocytes in the cortex away from the site of injury. CT and CS-PG were present in gray matter areas of the cortex that had been directly damaged during the implant procedure and in the corpus callosum when lesioned during implantation. In vitro, the glial tissue removed from the lesion site of neonatal animals supported neurite outgrowth, while scars removed from adult animals did not. The inability of the adult glial scar tissue to support neurite outgrowth was best correlated with the expression of CS-PG and CT, suggesting that these molecules may be involved in limiting the growth of regenerating axons in the CNS after injury.
Aggrecans↗