Osteochondral tissue transfers.
Explore the source record for details and available documents.
Cartilage, Articular↗
Biomedical subjects
R H Miller
Publications and source records attributed to R H Miller.
Contact with central nervous system myelin inhibits oligodendrocyte progenitor maturation.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are generated during development through the proliferation and differentiation of a distinct progenitor population. Not all oligodendrocyte progenitors generated during development differentiate, however, and large numbers of oligodendrocyte progenitors are present in the adult CNS, particularly in white matter. These "adult progenitors" can be identified through expression of the NG2 proteoglycan. Adult oligodendrocyte progenitors are thought to develop from the original pool of progenitors and in vitro are capable of differentiating into oligodendrocytes. Why these cells fail to differentiate in the intact CNS is currently unclear. Here we show that contact with CNS myelin inhibits the maturation of immature oligodendrocyte progenitors. The inhibition of oligodendrocyte progenitor maturation is a characteristic of CNS myelin that is not shared by several other membrane preparations including adult and neonatal neural membrane fractions, PNS myelin, or liver. This inhibition is concentration dependent, is reversible, and appears not to be mediated by either myelin basic protein or basic fibroblast growth factor. Myelin-induced inhibition of oligodendrocyte progenitor maturation provides a mechanism to explain the generation of a residual pool of immature oligodendrocyte progenitors in the mature CNS.
Animals↗
Rat optic nerve oligodendrocytes develop in the absence of viable retinal ganglion cell axons.
Retinal ganglion cell axons and axonal electrical activity have been considered essential for migration, proliferation, and survival of oligodendrocyte lineage cells in the optic nerve. To define axonal requirements during oligodendrogenesis, the developmental appearance of oligodendrocyte progenitors and oligodendrocytes were compared between normal and transected optic nerves. In the absence of viable axons, oligodendrocyte precursors migrated along the length of the nerve and subsequently multiplied and differentiated into myelin basic protein-positive oligodendrocytes at similar densities and with similar temporal and spatial patterns as in control nerves. Since transected optic nerves failed to grow radially, the number of oligodendrocyte lineage cells was reduced compared with control nerves. However, the mitotic indices of progenitors and the percentage of oligodendrocytes undergoing programmed cell death were similar in control and transected optic nerves. Oligodendrocytes lacked their normal longitudinal orientation, developed fewer, shorter processes, and failed to form myelin in the transected nerves. These data indicate that normal densities of oligodendrocytes can develop in the absence of viable retinal ganglion axons, and support the possibility that axons assure their own myelination by regulating the number of myelin internodes formed by individual oligodendrocytes.
Animals↗
Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus.
The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus. Four chimpanzees were immunized with 1 of 2 licensed recombinant hepatitis B vaccines. Shortly after the chimpanzees developed antibodies to hepatitis B surface antigen (anti-HBs), they were challenged intravenously with mutant HBV strain AS. Two unvaccinated chimpanzees served as positive controls. The 4 vaccinated chimpanzees did not develop evidence of HBV infection or hepatitis during 2 years following virus challenge. In contrast, the 2 unvaccinated chimpanzees developed HBV infection and hepatitis. Serum anti-HBs in the vaccinated chimpanzees reacted not only with wild-type surface antigen, but also with mutant surface antigen by competition enzyme-linked immunosorbent assay (ELISA). Thus, immunization of chimpanzees with licensed recombinant hepatitis B vaccines stimulates anti-HBs that is broadly reactive and affords protection against infection with a surface gene mutant of HBV, suggesting that properly immunized individuals are not at significant risk of infection with this prototype variant strain of HBV.
Animals↗
Mechanisms of oligodendrocyte commitment in the vertebrate CNS.
Explore the source record for details and available documents.
Animals↗
Misclassification and selection bias when identifying Alzheimer's disease solely from Medicare claims records.
BACKGROUND: Medicare claims as the basis for health condition adjustments is becoming a method of choice in capitation reimbursement. A recent study has found that claims-based beneficiary classification for Alzheimer's disease produces lower prevalence estimates and higher average costs than previous healthcare cost studies in this population. These sets of studies differ in data sources, period length, and in their specification of dementia. OBJECTIVES: Participants in the Medicare Alzheimer's Disease Demonstration (MADDE) provide a sample of persons known to have some form of dementia. This group is used to test the adequacy of claims data for identifying eligible cases and any bias in expenditure differences between those flagged or not flagged by a claim in a given period. DESIGN: A prospective cohort design using up to 36 months of claims data. SETTING: The demonstration enrolled 4166 participants in treatment, and 3942 in a control group in eight communities across the US. Cases were combined in this analysis. PARTICIPANTS: Persons with available Medicare Part A & B claims data: those receiving care under fee for service reimbursement were used in the analysis. A total of 5379 MADDE cases received fee for service care during 1991 and 1992, the period of primary interest in the analysis. MEASUREMENT: Client health and functional status interviews and Medicare Part A & B claims. RESULTS: Less than 20% of MADDE participants were classified with Dementia of the Alzheimer type (DAT) from a single year of claims although 68% had a DAT diagnosis from a referring physician. Annualized expenditures were 1.7 times higher among those with DAT from claims compared with those known otherwise to have dementia but who had not been identified with this condition from Medicare claims. CONCLUSION: Underclassification of dementia from claims records can be partially remedied by increasing the period during which claims are compiled, but additional diagnostic sources will likely be needed to increase prevalence counts closer to 100% of true cases. Risk adjustment based on a single year of reported claims expenditures may overpay providers, at least in the short term, because payment incentives will likely increase prevalence reporting.
Aged↗
Managed care and medical injury: let's not throw out the baby with the backlash.
Explore the source record for details and available documents.
Attitude to Health↗
Sonic hedgehog signaling is required during the appearance of spinal cord oligodendrocyte precursors.
Spinal cord oligodendrocyte precursors arise in the ventral ventricular zone as a result of local signals. Ectopic oligodendrocyte precursors can be induced by sonic hedgehog (Shh) in explants of chick dorsal spinal cord over an extended developmental period. The role of Shh during normal oligodendrocyte development is, however, unclear. Here we demonstrate that Shh is localized to the ventral spinal cord immediately prior to, and during the appearance of oligodendrocyte precursors. Continued expression of Shh is required for the appearance of spinal cord oligodendrocyte precursors as neutralization of Shh signaling both in vivo and in vitro during a defined developmental period blocked their emergence. The inhibition of oligodendrocyte precursor emergence in the absence of Shh signaling was not the result of inhibiting precursor cell proliferation, and the neutralization of Shh signaling after the emergence of oligodendrocyte precursors had no effect on the appearance of additional cells or their subsequent differentiation. Similar concentrations of Shh induce motor neurons and oligodendrocytes in dorsal spinal cord explants. However, in explants from early embryos the motor neuron lineage is preferentially expanded while in explants from older embryos the oligodendrocyte lineage is preferentially expanded.
Animals↗
Initial report of primary sinusitis caused by an atypical pathogen (Mycobacterium chelonae) in an immunocompetent adult.
Primary sinonasal infections caused by atypical mycobacteria are rare. In fact, only four examples of a primary nontuberculous mycobacterial etiology of paranasal sinusitis have been cited in the literature. The patients in all these cases were infected with the human immunodeficiency virus and, by definition, they all had acquired immunodeficiency syndrome. We present a report of an immunocompetent adult with a history of chronic sinusitis who consistently and repeatedly manifested a fast-growing, nonpigmented, atypical mycobacterium of the Runyon group IV category: Mycobacterium chelonae. The patient was successfully treated over a 3-year period with a combination of antimicrobial agents, multiple limited endoscopic sinus surgeries, and eventually a total globe-sparing maxillectomy. At this time, the patient is disease-free and has received no further treatment. This case represents the first report of an immunocompetent adult host with a primary atypical mycobacterial infection of the paranasal sinuses. It also demonstrates the multimodal nature of the treatment of atypical mycobacterial infections. We also discuss the Byzantine classification scheme relative to atypical mycobacteria, the disease process in the immunocompromised host, and the various treatment options.
Adult↗
Effect of enalapril on blood pressure, renal function, and the renin-angiotensin-aldosterone system in cats with autosomal dominant polycystic kidney disease.
OBJECTIVE: To evaluate blood pressure, renal function, and the renin-angiotensin-aldosterone system (RAAS) in cats with autosomal dominant polycystic kidney disease (ADPKD) and to assess the effect of enalapril on these variables. ANIMALS: 6 cats with ADPKD and 6 age-matched healthy cats. PROCEDURE: To measure blood pressure and heart rate, a radiotelemetry catheter was placed in the left femoral artery of each cat. Baseline data collection included 24-hour blood pressure, heart rate, and motor activity. Blood was then collected for analysis of RAAS status and renal function. Enalapril (0.5 mg/kg of body weight, p.o., q 24 h) was administered for 1 week, and data collection was repeated. RESULTS: Differences in baseline blood pressure, heart rate, motor activity, RAAS status, and renal function were not detected between cats with ADPKD and control cats. Hypertension was not documented in cats with ADPKD. Blood pressure was significantly reduced for 15 to 17 hours after treatment with enalapril in both groups. Administration of enalapril also resulted in significant increases in plasma renin activity and significant decreases in angiotensin converting enzyme activity and atrial natriuretic peptide concentration but only minimal changes in glomerular filtration rate and effective renal plasma flow in both groups of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Although hypertension is common in humans with ADPKD, cats with ADPKD were normotensive. Treatment with enalapril (0.5 mg/kg, p.o., q 24 h) significantly reduced blood pressure in normotensive healthy cats and cats with ADPKD, and resulted in predictable changes in RAAS enzyme activities and hormone concentrations. Enalapril had minimal effects on renal function.
Animals↗
The chemokine growth-regulated oncogene-alpha promotes spinal cord oligodendrocyte precursor proliferation.
Chemokines, (chemotactic cytokines) are a family of regulatory molecules involved in modulating inflammatory responses. Here we demonstrate that the chemokine growth-regulated oncogene-alpha (GRO-alpha) is a potent promoter of oligodendrocyte precursor proliferation. The proliferative response of immature spinal cord oligodendrocyte precursors to their major mitogen, platelet derived growth factor (PDGF), is dramatically enhanced by GRO-alpha present in spinal cord conditioned medium. One source of GRO-alpha is a subset of spinal cord astrocytes. Cultures of astrocytes contain GRO-alpha mRNA and protein and secrete biologically active concentrations of GRO-alpha. In postnatal spinal cord white matter the location of GRO-alpha-immunoreactive cells is developmentally regulated: GRO-alpha+ cells first appear in ventral and later in dorsal spinal cord white matter. These results suggest that localized proliferation of oligodendrocytes is mediated by synergy between PDGF and GRO-alpha.
Animals↗
Demyelination in the central nervous system mediated by an anti-oligodendrocyte antibody.
The factors responsible for the major demyelinating disease of the central nervous system (CNS), multiple sclerosis, are poorly defined. Although T-cell-mediated immune responses play a pivotal role in establishing the inflammatory response, humoral factors also may be critical in disease progress. We have isolated a mouse monoclonal antibody (mAb 2B10) that recognizes a cell-surface molecule expressed exclusively by rat oligodendrocytes, the cells responsible for the formation and maintenance of CNS myelin. In cultures of neonatal rat spinal cord, mAb 2B10 specifically mediated oligodendrocyte cell death in the absence of complement. In the current study, mAb 2B10-producing hybridoma cells were implanted into adult rat brain ventricles, and the effect of mAb 2B10 on CNS cytoarchitecture was examined. In the optic nerves of mAb 2B10-treated animals, there was significant focal myelin degeneration near the optic chiasm. Axons in the myelin degenerate regions were largely healthy. There was no significant infiltration of hematopoietic-derived cells into the affected regions, but microglia were activated focally and phagocytosed the collapsed myelin. This study demonstrates that an antibody directed against myelin-forming cells induces CNS demyelination and supports the hypothesis that autoantibodies may play a role in CNS demyelinating diseases.
Animals↗
Lessons from the cat: feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1.
Explore the source record for details and available documents.
AIDS Vaccines↗
Morphological analysis of the early stages of oligodendrocyte development in the vertebrate central nervous system.
Oligodendrocytes are responsible for myelin formation in the vertebrate central nervous system. While in vitro analysis have provided critical information on the cellular properties of oligodendrocyte precursors, they provide limited information on the morphological development of these cells in the intact CNS. Recent studies have begun to provide insights into when and where oligodendrocyte precursors arise in the neural tube. In the chick CNS, the monoclonal antibody O4 selectively labels oligodendrocyte lineage cells both in vitro and in vivo and here we discuss the characteristics of O4+ oligodendrocyte precursors during development of the chick CNS. The earliest oligodendrocytes initially develop in restricted locations in the CNS. In the spinal cord, for example, oligodendrocyte precursors arise in the ventral ventricular zone dorsal to the floor plate. These early oligodendrocyte precursors are integral components of the lining of the central canal and have an embryonic neuroepithelial cell morphology, suggesting that commitment to the oligodendrocyte lineage occurs in the ventricular zone. With maturation these early oligodendrocyte precursors lose their ventricular connection, adopt a uni- or-bipolar morphology, and migrate throughout the CNS. When these cells reach presumptive white matter, they stop migrating, become multiprocessed, and differentiate into immature oligodendrocytes. The maturation of these newly formed oligodendrocytes results in the upregulation of expression of a variety of myelin specific genes such as MBP and PLP and the subsequent elaboration of the myelin organelle. In the developing optic nerve, the onset of myelination occurs several days after oligodendrocyte precursors populate the nerve, suggesting that additional signals are required to induce myelin formation.
Animals↗
Antibody-mediated oligodendrocyte cell death requires an astrocyte-derived cosignal.
We have described a monoclonal antibody (mAb), 2B10, that identifies a cell-surface protein expressed only on oligodendrocytes, the myelin-forming cells in the vertebrate central nervous system. To examine the effect of mAb 2B10 on oligodendrocyte development and survival, purified antibody was added to dissociated cultures of neonatal rat spinal cord. Addition of mAb 2B10 induced significant cell death, with a reduction of approximately 70% in the number of differentiated oligodendrocytes. The number of astrocytes was unaltered. Addition of mAb 2B10 did not affect the proliferation or differentiation of oligodendrocyte precursors. MAb 2B10-induced death of differentiated oligodendrocytes was independent of complement but did require an environmental signal. In purified oligodendrocyte cultures, binding of the antibody to oligodendrocytes did not induce cell death. Conditioned medium and transwell coculture experiments indicated that the required environmental signals were not soluble. By contrast, when oligodendrocytes were cocultured with astrocytes, addition of mAb 2B10 specifically induced cell death of differentiated oligodendrocytes, suggesting that a locally acting cosignal from astrocytes was required to facilitate the cell death. This cosignal was provided by live astrocytes but not by fixed astrocytes, microglia, or fibroblasts. Such antibody-induced oligodendrocyte cell death may explain in part the loss of myelin-forming cells in demyelination conditions, such as multiple sclerosis.
Animals↗
Titration of recombinant woodchuck hepatitis virus DNA in adult woodchucks.
In vivo transfection of Eastern woodchucks (Marmota monax) with recombinant woodchuck hepatitis virus (WHV) DNA is effective in inducing virus infection for the study of replication, pathogenicity, and oncogenicity of wild-type and mutated WHV. The one drawback to this procedure is the need for preparation of large amounts of WHV DNA. Reduction of the amount of WHV DNA in the transfection protocol necessary to induce infection would save considerable time and resources. Therefore, we conducted a titration of WHV DNA, ranging from 50 micrograms to 50 pg of DNA, in adult woodchucks to determine the minimum infectious dose of recombinant WHV DNA. As little as 50 ng of transfected WHV DNA induced productive infection in adult woodchucks. Thus, transfection with large amounts of recombinant WHV DNA appears to be unnecessary.
Animals↗
Homotypic cell contact-dependent inhibition of astrocyte proliferation.
The normal adult vertebrate nervous system is a relative quiescent tissue in terms of cell proliferation. However, astrocytes in many regions of the central nervous system (CNS) retain the capacity to undergo cell division. To examine the mechanisms that regulate the proliferation of astrocytes in the CNS we have utilized an in vitro assay in which astrocyte density and cellular environment could be regulated. We demonstrate that type 1 astrocytes derived from the cerebral cortex of developing rats exhibit a profound density-dependent inhibition of proliferation. This inhibition of proliferation was cell type specific, but not restricted to type 1 astrocytes. NIH 3T3 cells but not smooth muscle cells inhibited astrocyte proliferation, while contact-inhibited astrocytes did not inhibit oligodendrocyte proliferation. Co-culture of type 1 astrocytes with neurons from a variety of sources resulted in induction of a process-bearing astrocyte morphology and promoted glial cell proliferation. Thus, induction of a process-bearing astrocyte morphology does not lead to a cessation of proliferation. The inhibition of astrocyte proliferation did not appear to be mediated through the release or sequestration of soluble factors but rather could be induced by membrane-associated factors.
Animals↗
Regulation of oligodendrocyte development.
Oligodendrocytes are the cells responsible for the formation of myelin in the central nervous system. Recent studies demonstrated that cells of the oligodendrocyte lineage initially arise in distinct regions of the ventricular zone during early development. These cells or their progeny migrate to developing white matter tracts where they undergo the majority of their proliferation and subsequently differentiate into myelinating cells. Oligodendrocyte-precursor cell proliferation is regulated by a number of distinct growth factors that act at distinct stages in the lineage and the final number of oligodendrocytes in any region of the CNS is regulated by local influences. A density-dependent feedback inhibition of proliferation reduces the responsiveness of the cells to their growth factors and the final matching of oligodendrocyte and axon number is accomplished through the local regulation of cell death. In this review, we discuss the major factors that regulate three distinct stages in the development of the oligodendrocyte lineage: The initial induction of oligodendrocyte progenitors, the regulation of expansion and dispersion of the committed precursor cell population, and the final regulation of oligodendrocyte precursor number through the local inhibition of oligodendrocyte precursor proliferation and cell death.
Animals↗