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Biomedical subjects

J Silver

Publications and source records attributed to J Silver.

At least 55 records · Page 3Linked to original sources
PubMed1999

Reduced bacterial dissemination and liver injury in CD14-deficient mice following a chronic abscess-forming peritonitis induced by Bacteroides fragilis.

The CD14 myelomonocytic differentiation antigen plays a major role in acute Gram-negative infections with Escherichia coli; however, its role in chronic infections has not yet been analyzed. To address this question, we studied the role of CD14 in a chronic abscess-forming peritonitis, induced by Bacteroides fragilis. B. fragilis (3x10(8) CFU/ml) were resuspended in a liquid nutrient agar and injected into the peritoneal cavity of CD14-deficient (CD 14-/-) and normal C57BL/6J (CD 14+/+) mice, respectively. After 3 days there was a severe phlegmonous intra-abdominal inflammation in both groups. After 7 days an abscess-forming peritonitis developed and by 14 days the infectious foci were compartimentalized. These observations were indistinguishable between CD14-/- and CD14+/+ mice. Although no differences were seen in abscess formation, CD14-/- mice were able to clear B. fragilis more efficiently from the blood than CD14+/+ mice. After 3, 7, and 14 days blood cultures were B. fragilis positive in 11% (1/9), 20% (2/10), and 0% (0/9) in CD14-/-compared with 90% (9/10), 78% (7/9), and 20% (2/10) in CD14+/+ mice, respectively (P<0.05). Furthermore, although the infection resulted in hepatocellular necrosis and severe hepatitis in both groups, at day 14 the liver cell damage was more severe in CD14+/+ than in CD14-/- mice (P<0.05). These results show that the chronic abscess formation induced by B. fragilis capsular polysaccharides is CD14 independent; however, bacterial clearance and/or dissemination and liver cell damage are at least partially influenced by CD14-dependent mechanisms.

Abscess↗
PubMed1999

Paediatric community vision screening--a new model.

The purpose of this study was to establish if a community based model using a Hospital Optometrist and Community Orthoptist can provide a practical secondary vision screening service for children. These professionals working in an Inner London Health Centre, assessed children who had failed primary vision screening. In total 483 new patients were seen between April 1994 and March 1996 with the largest referral source being the school nurse screening programme. The majority were managed by the team with a total onward referral rate to the Hospital Eye Service of 14%. In 78% of these cases the consultant's diagnosis agreed with the reason for referral. Where the consultant's diagnosis differed the children were identified as normal or a variant of normal. This model of care provides a 'one stop service' where a child identified as having a potential visual problem at primary screening can be assessed, refracted and provided with spectacles in a local setting without hospital referral. Referrals to the Hospital Eye Service are considerably reduced and a convenient service is provided for parents and children.

Age Distribution↗
PubMed1999

Regulation of the parathyroid hormone gene by vitamin D, calcium and phosphate.

Secondary hyperparathyroidism is a frequent complication of chronic renal failure resulting in severe bone disease. Secondary hyperparathyroidism is composed of increased in parathyroid hormone (PTH) synthesis and secretion due to an increase in PTH gene expression and parathyroid cell proliferation. PTH gene expression is regulated by calcium, phosphate and 1,25-dihydroxy vitamin D (1,25(OH)2D). 1,25(OH)2D3 injected to rats leads to a dramatic decrease in PTH gene transcription without any increase in serum calcium. Hypocalcemia leads to a large increase in PTH mRNA levels which is post-transcriptional. Hypophosphatemia leads to a marked decrease in PTH gene expression that is also post-transcriptional. The mechanisms of the post-transcriptional effects of calcium and phosphate on the PTH gene have shown to be due to changes in protein-RNA interactions at the PTH mRNA 3'-UTR. Hypocalcemia leads to increased binding of parathyroid cytosolic proteins to the PTH mRNA 3'-UTR and hypophosphatemia to decreased binding of these proteins to the PTH mRNA 3'-UTR. The binding of the parathyroid proteins stabilizes the PTH RNA in an in vitro degradation assay. In rats with experimental uremia due to 5/6 nephrectomy, there is an increase in PTH mRNA levels due to a decrease in degradation of the PTH RNA as determined by this assay. The characterization of the parathyroid cytosolic proteins that interact with the PTH mRNA 3'-UTR may lead to a clearer understanding of how changes in serum calcium and phosphate result in secondary hyperparathyroidism.

3' Untranslated Regions↗
PubMed1999

Vitamin D and the parathyroid.

Vitamin D's biologically active metabolite, 1,25(OH)2D3, has important effects upon the parathyroid cell that are relevant to both the physiology of mineral metabolism and the regulation of the secondary hyperparathyroidism of chronic renal failure. 1,25(OH)2D3 markedly decreases parathyroid hormone (PTH) gene transcription and thus PTH synthesis and secretion. It also acts to decrease parathyroid cell proliferation. Nonhypercalemic analogs of 1,25(OH)2D3 are being developed that may have a wider therapeutic window than 1,25(OH)2D3 itself. In the situations of chronic hypocalcemia and hypophosphatemia, there are interesting interrelationships between 1,25(OH)2D3 and the post-transcriptional regulation of the PTH gene. In nodular secondary hyperparathyroidism, there is down-regulation of the vitamin D receptor in the parathyroid. Different vitamin D receptor genotypes may be associated with higher levels of serum PTH and a predisposition to autonomous hyperplasia.

Cell Division↗
PubMed1999

Mechanism of increased parathyroid hormone mRNA in experimental uremia: roles of protein RNA binding and RNA degradation.

Patients with chronic renal failure develop secondary hyperparathyroidism with increased synthesis and secretion of parathyroid hormone (PTH) resulting in severe skeletal complications. In rats with secondary hyperparathyroidism due to 5/6 nephrectomy, there are increased PTH mRNA levels, and this mechanism was studied. Parathyroid glands were microdissected from control and 5/6 nephrectomy rats and analyzed for PTH mRNA and control genes, and the nuclei were used for nuclear run-on experiments. The cytosolic proteins of the parathyroids were used to study PTH mRNA protein binding by ultraviolet cross-linking and the degradation of the PTH transcript in vitro. Nuclear run-ons showed that the increase in PTH mRNA levels was posttranscriptional. Protein binding to the PTH mRNA 3'-UTR determines PTH mRNA stability and levels. Parathyroid proteins from uremic rats bound PTH mRNA similar to control rats by ultraviolet cross-linking. To determine the effect of uremia on PTH mRNA stability, an in vitro RNA degradation assay was performed with parathyroid proteins from uremic rats. When parathyroid proteins from control rats were incubated with PTH mRNA, there was transcript degradation already at 30 min, reaching 50% at 60 min and 90% at 180 min. With uremic parathyroid proteins, the PTH mRNA was not degraded at all at 120 min and was moderately decreased at 180 min. This decrease in degradation by uremic parathyroid proteins suggests a decrease in parathyroid cytosolic endonuclease activity in uremia resulting in a more stable PTH transcript. The increased PTH mRNA levels would translate into increased PTH synthesis and serum PTH levels, which would lead to metabolic bone disease in many patients with chronic renal failure.

3' Untranslated Regions↗
PubMed1998

A role for tectal midline glia in the unilateral containment of retinocollicular axons.

Retinal fibers approach close to the tectal midline but do not encroach on the other side. Just before the entry of retinal axons into the superior colliculus (SC), a group of radial glia differentiates at the tectal midline; the spatiotemporal deployment of these cells points to their involvement in the unilateral containment of retinotectal axons. To test for such a barrier function of the tectal midline cells, we used two lesion paradigms for disrupting their radial processes in the neonatal hamster: (1) a heat lesion was used to destroy the superficial layers of the right SC, including the midline region, and (2) a horizontally oriented hooked wire was inserted from the lateral edge of the left SC toward the midline and was used to undercut the midline cells, leaving intact the retinorecipient layers in the right SC. In both cases, the left SC was denervated by removing its contralateral retinal input. Animals were killed 12 hr to 2 weeks later, after intraocular injections of anterograde tracers to label the axons from the remaining eye. Both lesions resulted in degeneration of the distal processes of the tectal raphe glia and in an abnormal crossing of the tectal midline by retinal axons, leading to an innervation of the opposite ("wrong") tectum. The crossover occurred only where glial cell attachments were disrupted. These results document that during normal development, the integrity of the midline septum is critical in compartmentalizing retinal axons and in retaining the laterality of the retinotectal projection.

Animals↗
PubMed1998

Complement depletion reduces macrophage infiltration and activation during Wallerian degeneration and axonal regeneration.

After peripheral nerve injury, macrophages infiltrate the degenerating nerve and participate in the removal of myelin and axonal debris, in Schwann cell proliferation, and in axonal regeneration. In vitro studies have demonstrated the role serum complement plays in both macrophage invasion and activation during Wallerian degeneration of peripheral nerve. To determine its role in vivo, we depleted serum complement for 1 week in adult Lewis rats, using intravenously administered cobra venom factor. At 1 d after complement depletion the right sciatic nerve was crushed, and the animals were sacrificed 4 and 7 d later. Macrophage identification with ED-1 and CD11a monoclonal antibodies revealed a significant reduction in their recruitment into distal degenerating nerve in complement-depleted animals. Complement depletion also decreased macrophage activation, as indicated by their failure to become large and multivacuolated and their reduced capacity to clear myelin, which was evident at both light and electron microscopic levels. Axonal regeneration was delayed in complement-depleted animals. These findings support a role for serum complement in both the recruitment and activation of macrophages during peripheral nerve degeneration as well as a role for macrophages in promoting axonal regeneration.

Animals↗
PubMed1998

The periodontopathogen Porphyromonas gingivalis binds iron protoporphyrin IX in the mu-oxo dimeric form: an oxidative buffer and possible pathogenic mechanism.

Mössbauer spectroscopy was used to re-evaluate iron protoporphyrin IX, FePPIX, binding and the chemical nature of the black iron porphyrin pigment of Porphyromonas gingivalis. We demonstrate that FePPIX is bound to the cell in the mu-oxo dimeric form, [Fe(III)PPIX]2O, and that the iron porphyrin pigment is also composed of this material. P. gingivalis also assimilated monomeric Fe(II)- and Fe(III)PPIX into mu-oxo dimers in vitro. Scatchard analysis revealed a greater binding maximum of cells for mu-oxo dimers than for monomeric Fe(III)-or Fe(II)PPIX, although the relative affinity constant for the dimers was lower. Formation of [Fe(III)PPIX]2O via reactions of Fe(II)PPIX with oxygen, and its toxic derivatives, would serve as an oxidative buffer and permit P. gingivalis and other black-pigmenting anaerobes to engender and maintain a local anaerobic environment. Tying up of free oxygen species with iron protoporphyrin IX would also reduce and limit Fe(II)PPIX-mediated oxygen-radical cell damage. More importantly, formation of a cell-surface mu-oxo dimer layer may function as a protective barrier against assault by reactive oxidants generated by neutrophils. Selective interference with these mechanisms would offer the possibility of attenuating the pathogenicity of P. gingivalis and other iron protoporphyrin IX-binding pathogens whose virulence is regulated by this reactive molecule.

Anaerobiosis↗
PubMed1998

RNA-Protein binding and post-transcriptional regulation of parathyroid hormone gene expression by calcium and phosphate.

Parathyroid hormone (PTH) regulates serum calcium and phosphate levels, which, in turn, regulate PTH secretion and mRNA levels. PTH mRNA levels are markedly increased in rats fed low calcium diets and decreased after low phosphate diets, and this effect is post-transcriptional. Protein-PTH mRNA binding studies, with parathyroid cytosolic proteins, showed three protein-RNA bands. This binding was to the 3'-untranslated region (UTR) of the PTH mRNA and was dependent upon the terminal 60 nucleotides. Parathyroid proteins from hypocalcemic rats showed increased binding, and proteins from hypophosphatemic rats decreased binding, correlating with PTH mRNA levels. There is no parathyroid cell line; however, a functional role was provided by an in vitro degradation assay. Parathyroid proteins from control rats incubated with a PTH mRNA probe led to an intact transcript for 40 min; the transcript was intact with hypocalcemic proteins for 180 min and with hypophosphatemic proteins only for 5 min. A PTH mRNA probe without the 3'-UTR, or just the terminal 60 nucleotides, incubated with hypophosphatemic proteins, showed no degradation at all, indicating that the sequences in the 3'-UTR determine PTH mRNA degradation. Hypocalcemia and hypophosphatemia regulate PTH gene expression post-transcriptionally. This correlates with binding of proteins to the PTH mRNA 3'-UTR, which determines its stability.

Animals↗
PubMed1998

Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease.

We have developed an in vitro model in which isolated senile plaque (SP) cores are presented to rat microglial cells in culture. Microglia rapidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppressed, allowing the SPs to persist. Suppression of phagocytosis by astrocytes appears to be a general phenomena since microglia in the presence of astrocytes showed reduced capacity to phagocytose latex beads as well. The astrocyte effect on microglia is related in part to a diffusible factor(s) since astrocyte- but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clearance of SP material allowing them to persist in Alzheimer's disease.

Alzheimer Disease↗
PubMed1998

Public policy update.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗