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Biomedical subjects

R H Miller

Publications and source records attributed to R H Miller.

At least 55 records · Page 3Linked to original sources
PubMed1998

Evidence for a bidirectional promoter complex within the X gene of woodchuck hepatitis virus.

The genetic organization of hepadnaviruses is unusual in that all cis-acting regulatory sequences are located within genes. Thus, in the mammalian hepadnavirus genome, the presurface, surface, and X transcript promoters reside within the polymerase gene while the pregenome transcript promoter is located within the X gene. In this study we have identified two additional promoters within the woodchuck hepatitis virus (WHV) X gene that stimulate production of transcripts in vitro. First, we cloned regions of the WHV X gene into a promoterless expression vector (pGL2) to examine their ability to promote expression of firefly luciferase and mapped a previously unidentified promoter to positions 1475-1625 of the WHV8 genome. Deletion analysis revealed that the essential domain of this promoter, termed the ORF5/deltaX transcript promoter, mapped to nucleotides 1525-1625. Analysis revealed that this transcript initiated at nucleotide 1572 in both human (HuH-7) and woodchuck (WLC-3) hepatoma cell lines. Consistent with this finding, DNA footprinting analysis revealed protection of nucleotides 1567-1578 on the positive strand of the WHV8 genome. The function of this transcript in vivo is unclear, however, it may be used to produce a truncated form of the X protein that initiates at an AUG codon at position 1743-1745 on the WHV8 genome. Next, a second promoter was identified at positions 1625-1975 that was responsible for production of an antisense transcript. The activity of this promoter was comparable to that of the previously characterized surface transcript promoter of WHV in the absence of an enhancer. The antisense transcript promoter resides immediately upstream of open reading frame (ORF) 6, a previously identified ORF on the strand opposite of the known WHV protein-encoding sequences, that is thought to represent a vestigial gene. Analysis indicates that the antisense transcript had multiple start sites: nucleotides 1683 and 1762 on the WHV8 genome when assayed in HuH-7 cells, and nucleotide 1786 when assayed in WLC-3 cells. These data are consistent with footprinting analysis of supercoiled WHV DNA that revealed that the regions encompassing nucleotides 1696-1685, 1781-1766, and 1801-1787 on the negative sense DNA strand were protected from nuclease degradation. It is possible that such a transcript was once used in protein expression in an ancestral virus and may now be used for genetic control of WHV replication and/or gene expression. Overall, these data are consistent with the presence of a bidirectional promoter complex within the WHV X gene.

Animals↗
PubMed1998

Dr. Miller goes to Washington: you should, too.

Otolaryngologists, like most physicians, tend to avoid local, state, and national politics for a variety of reasons. Although physicians and their patients are frequently affected by policies made in these political arenas, physicians tend to avoid active participation because of inexperience, lack of time, lack of knowledge about ways to influence policy development, and a general distaste for the political process. Otolaryngologists need to participate in the process to ensure that their particular perspectives and concerns are heard. However, otolaryngologists also need to look beyond their personal or specialty interests to influence the broader health care debate. Before we are specialists, we are first physicians who have a fiduciary responsibility to mankind (our patients) to improve the health care system for all Americans. We have a moral and ethical obligation to address, influence, and support health care beyond the specialty level. Health policy developed in an absence of physician input is missing the insight of expertise and experience.

Health Planning↗
PubMed1998

The impact of financial incentives on quality of health care.

Purchasers of health care could offer financial incentives to plans or providers in order to increase quality. Unfortunately, the current health care market, in which quality is rarely measured and there is no risk adjustment, actively discourages both plans and providers from maximizing quality, resulting in a poor overall level of quality, both in fee-for-service arrangements and health maintenance organizations. Health plans and providers will not focus on quality until mechanisms to correct for risk differences among enrollees can be developed. Although such risk adjustment will be the most important stimulus for quality, it should also be linked to improvements in information systems and agreement on a minimum benefits package, quality reporting standards, and financial solvency requirements.

Delivery of Health Care↗
PubMed1998

Detection of putative loci affecting conformational type traits in an elite population of United States Holsteins using microsatellite markers.

Quantitative trait loci affecting conformational type traits were studied in seven large grandsire families of US Holsteins using the granddaughter design and 16 microsatellite markers on 10 chromosomes. The most significant marker effect was marker BM203 (chromosome 27) for dairy form in a single grandsire family. A multivariate analysis for dairy form and milk yield was also conducted, and the result was highly significant, indicating that a segregating quantitative trait locus or loci affecting dairy form and milk yield could exist near BM203 on chromosome 27. Marker BM1258 (chromosome 23) had a significant effect on udder depth. A multivariate analysis on udder depth and somatic cell score was conducted for markers 513 and BM1258, and both markers showed significant effects on these two traits, indicating that one or several quantitative trait loci affecting udder depth and mastitis might exist on chromosome 23. Marker BM4204 (chromosome 9) had a significant effect on foot angle and on the composite index of traits pertaining to feet and legs, indicating that one or several quantitative trait loci affecting traits pertaining to feet and legs might exist on chromosome 9. Selection on these markers could increase genetic progress within these families.

Animals↗
PubMed1998

Detection of putative loci affecting milk production and composition, health, and type traits in a United States Holstein population.

Quantitative trait loci affecting milk yield and composition, health, and type traits were studied for seven large grandsire families of US Holstein using the granddaughter design. The families were genotyped at 20 microsatellite markers on 15 chromosomes, and the effects of the marker alleles were analyzed for 28 traits (21 type traits, 5 milk yield and composition traits, somatic cell score, and productive herd life). Markers BM415 on chromosome 6 and BM6425 on chromosome 14 were associated with effects on protein percentage in a single grandsire family. The latter marker had a lower probability of being associated with changes in milk yield and fat percentage in the same family. Increases in productive herd life were associated with an allele at marker BM719 on chromosome 16 in one grandsire family.

Animals↗
PubMed1998

Frontal sinus fractures.

Frontal sinus fractures usually occur in trauma situations involving substantial force and are frequently accompanied by other, sometimes life threatening, injuries. Early recognition of this injury is important to prevent serious complications as well as to restore cosmesis. This paper reviews the incidence, pathophysiology, classification, and controversial management of frontal sinus fractures.

Adolescent↗
PubMed1998

Healthcare organizational change: implications for access to care and its measurement.

OBJECTIVES: To summarize evidence from peer-reviewed literature on access to care for vulnerable HMO enrollee populations; to discuss the potential effect of recent HMO and physician organization changes on access to care and its measurement. STUDY DESIGN: Review and summary of peer-reviewed literature for two HMO populations: those with chronic conditions and diseases, and those subject to discrimination due to income, color, or ethnic background. I also reviewed and summarized literature on three major changes in capitated organizations (HMOs and capitated physician organizations) that could affect access to care for vulnerable populations, and summarized findings from healthcare manager interviews conducted for several recent research projects on health system change. PRINCIPAL FINDINGS: Although mixed, there are enough negative results to raise some concerns about access to care for HMO enrollees with chronic conditions and diseases. Several emerging organizational changes have the potential to change access to care for the vulnerable HMO enrollees. The shift in cost-cutting from fragmented clinical management of specific services at a point in time toward more integrated clinical management of all services for specific types of patients across time may improve access to care, as may increased efforts to attract and retain HMO enrollees. The increased importance of capitated provider organizations within the health system may restrict access in some ways, and expand access in others. CONCLUSIONS: Organizational changes can affect both access to care and its measurement. More research is needed on the effects of these changes on access to care and quality of care. For researchers examining access to care for vulnerable HMO enrollee populations, these changes create challenges to determine the most appropriate measures of access to care, and the most appropriate organizations and organizational characteristics to measure. RELEVANCE TO CLINICAL PRACTICE, MANAGEMENT, AND/OR POLICY: Changes in market competition are leading to organizational changes that affect access to care for vulnerable HMO enrollee populations. Public and/or private policies that improve measurement and reporting can affect market competition and improve access to care.

Capitation Fee↗
PubMed1998

Evaluation of solitary thyroid nodules.

The yield of malignancy when evaluating solitary thyroid nodules can be significantly increased by following a stepwise approach. The gold standard is fine needle aspiration. A thorough history and physical, thyroid scintigraphy, as well as exogenous suppression therapy, aid clinicians to efficiently evaluate the abundance of solitary thyroid nodules and isolate those which are likely to be neoplastic.

Biopsy, Needle↗
PubMed1998

Vocal cord paralysis.

Vocal cord paralysis is a multifacted problem that affects patients of all ages and presents initially to a wide range of healthcare professionals. It can cause laryngeal dysfunction ranging from slight hoarseness to life-threatening airway obstruction. When confronted with a patient with new onset vocal cord paralysis, the physician should determine the etiology of the paralysis. Only after an accurate diagnosis, can restoration of laryngeal function be addressed. Peripheral lesions injuring the vagus nerve or its branches are responsible for 90% of all vocal cord paralysis. Etiologies include neoplasms, surgical iatrogenic injury, and blunt and penetrating trauma in the head, neck, and thorax. Thyroid surgery has historically been accountable for almost a third of reported unilateral vocal cord paralyses. However, recent review has demonstrated a dramatic reduction in this incidence to less than 5%. Numerous treatment options exist for patients with vocal cord paralysis. These treatments can drastically reduce the social and economic disability incurred by these patients.

Humans↗
PubMed1998

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a disease characterized by the growth of wart-like neoplasms anywhere along the aerodigestive tract. The etiologic agent is the human papillomavirus, of which 90 subtypes have been described. The age distribution of those affected appears to be a bimodal curve, with the first peak around 5 years of age and the second occurring in adults in the third decade of life. The mainstay of treatment is surgical resection to maintain an adequate airway; patients often require multiple surgeries. The epidemiology, pathogenesis, clinical features, and treatment options are discussed. Current evidence regarding prognosis and the multifactorial nature of pathogenesis are also reviewed.

Adult↗
PubMed1997

Spinal cord oligodendrocytes develop from a limited number of migratory highly proliferative precursors.

Oligodendrocytes are responsible for myelin formation in spinal cord white matter. In the mature spinal cord, the majority of white matter is localized peripherally. During early development, however, the first oligodendrocyte precursors arise in the ventral ventricular zone of the developing cord. Thus, prior to myelination, both migration and proliferation of oligodendrocyte precursors must occur. When and where these events occur is currently unclear. In the chick spinal cord, oligodendrocyte precursors express antigens recognized by the monoclonal antibody O4. Here we show that all chick spinal cord oligodendrocytes are derived from O4+ cells and all O4+ cells appear to give rise to oligodendrocytes. Analysis of the number and distribution of oligodendrocyte precursors in chick spinal cord at different stages of development suggests that relatively few cells migrate from the ventricular source which then proliferate extensively in white matter. This migration is guided by general dispersive cues. Clonal analysis of oligodendrocyte development in cultures derived from different regions of the rodent spinal cord indicated that the cells that initially populate dorsal and peripheral spinal cord retained similar clonal properties to those in ventral spinal cord, suggesting the migrating cells were immature, highly proliferative precursors. Consistent with these results, BrdU incorporation studies indicate that glial proliferation is extensive and persistent in postnatal rat spinal cord white matter. Together, these studies suggest that spinal cord white matter is initially populated by very immature precursors that then undergo extensive local proliferation prior to myelination.

Animals↗
PubMed1997

Notochord is essential for oligodendrocyte development in Xenopus spinal cord.

Oligodendrocyte precursors originate in the ventral ventricular zone of the developing spinal cord. To examine whether the notochord is essential for the development of oligodendrocytes in Xenopus spinal cord the notochord was prevented from forming, ablated, or transplanted during early stages of development. Differentiated oligodendrocytes did not appear in spinal cord regions lacking a notochord in animals in which notochord failed to develop after UV irradiation at the one-cell stage. Similarly, differentiated oligodendrocytes were not detected in the spinal cord adjacent to the site of segmental notochord ablation at embryonic or larval stages. Transplantation of an additional notochord dorsal to the spinal cord induced the premature appearance of differentiated oligodendrocytes in adjacent lateral and dorsal spinal cord white matter. These results indicate that the development of Xenopus spinal cord oligodendrocytes is dependent on local influences from the notochord and suggest that the notochord is essential for oligodendrocyte development in Xenopus spinal cord.

Animals↗
PubMed1997

Focal ventricular origin and migration of oligodendrocyte precursors into the chick optic nerve.

During central nervous system (CNS) development, oligodendrocyte precursors originate in specific locations and subsequently migrate to all regions of the CNS. Here, we demonstrate that the chick optic nerve is populated by oligodendrocyte precursors, which initially appeared in a focal region at the ventral midline of the third ventricle at stage 26-27. Oligodendrocyte precursors migrated into the chiasmal end of the nerve by stage 29 and became uniformly distributed by stage 35. Migrating precursors were restricted to the anterior region of the nerve, closely apposed to axons, and had a bipolar morphology. In contrast to the polysialic acid (PSA)-dependent cooperative streaming migration of olfactory neuronal precursors, the migration of oligodendrocyte precursors along the optic nerve appeared axophilic and unaffected by removal of neural cell adhesion molecule (N-CAM)-associated PSA. These data indicate that during development, defined domains of the ventricular zone give rise to distinct cell types that utilize discrete mechanisms to navigate specific migrational pathways.

Animals↗
PubMed1997

Infectivity and pathogenicity in chimpanzees of a surface gene mutant of hepatitis B virus that emerged in a vaccinated infant.

Hepatitis B virus (HBV) variants with amino acid mutations in the a epitope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of serum that contained the first such described HBV mutant, with an Arg-for-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/or biochemical evidence of hepatitis B. A polymerase chain reaction-based assay that discriminated between the wild type and mutant viral genomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in infection of the chimpanzees receiving these dilutions only with the mutant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, infectious, and pathogenic in chimpanzees.

Animals↗