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Biomedical subjects

D Korn

Publications and source records attributed to D Korn.

At least 19 recordsLinked to original sources
PubMed1999

The changing landscape for clinical research.

The authors review the history of U.S. clinical research and identify the profound changes stemming from advancements in the biomedical sciences, the recent transformation in the organization and financing of health care delivery, and the increasing application of information technologies. They observe that the enterprise must reorganize to account for the changed landscape, but there is a lack of the data necessary to monitor change and determine the extent to which clinical research is successfully realigning and sustaining itself. The authors discuss the evolving definition, scope, and venues for clinical research, and review previous analyses of clinical research's difficulties and remedies proposed: shared responsibility in the financing of academic medicine, support by federal and private health insurers for routine costs of patient care in clinical trials, and strengthened collaboration between and among industry, academia, insurers, and government. The authors conclude by describing two major initiatives to foster clinical investigation in the new landscape. The first is the Clinical Research Summit Project, a convocation of representative stakeholders from the health care system with an interest in clinical research, whose charge will be to formulate a national agenda for clinical research that has the broad-based support of the stakeholders. Among the challenges of this undertaking are the needs to identify new and stable sources of support for clinical research infrastructure, assess the future workforce needs for clinical investigation, and devise new methods to ensure the continued vitality and account-ability of clinical research. The second is the Clinical Research Task Force, an initiative of the Association of American Medical Colleges (AAMC), which is already exploring and advising on how AAMC member organizations can best strengthen their capacity to support clinical research programs in the current scientific, health care delivery, and financial environment.

Academic Medical Centers↗
PubMed1997

How medical schools can maintain quality while adapting to resource constraints.

To gain a better understanding of the effects on medical schools of ongoing transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) formed the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. Six working groups were appointed to address different issues of importance. This article is a report of the findings and recommendations of the Working Group on Adapting to Resource Constraints. That group was charged to consider how leaders in academic medicine can respond to the challenges of external forces and the anticipated diminishing of resources, and to focus on medical schools and how they can maintain quality while reengineering to effect needed changes. The group members developed their thinking within four categories: size of the academic enterprise; organizational models and their relationships to the clinical enterprise; faculty tenure and compensation; and partnerships with capital-intensive entities. Three recommendations for action, to which the APMOMS unanimously agreed, were made to the AAMC, which has already acted upon them in ways described in the article. The group also developed a series of "ideas for consideration," which represent a range of the members' perspectives. The working group did not seek (and probably could not have obtained) unanimous agreement on many of the issues that these ideas focus upon. The ideas are presented as a series of resolutions designed to stimulate discussion and foster better-informed planning.

Education, Medical↗
PubMed1997

On the cost of educating a medical student.

The cost of educating a medical student has been an issue of intermittent public concern for most of the twentieth century, beginning in 1910 with the Flexner Report. The issue is now reemerging as a topic of high public and political interest, for several reasons, including concern about medical schools and their financing. Estimates of medical student education costs appear to vary widely; but such variations derive from the different ways the question has been framed. Costs can be categorized as instructional costs and total educational resource costs. Instructional costs, which can be distinguished further as marginal costs or proportionate-share costs, are those costs that can be related directly to the teaching program and its support. Total educational resource costs are those costs supporting all faculty deemed necessary to conduct undergraduate medical education in all their activities of teaching, research, scholarship, and patient care. The authors review studies spanning a period of more than 20 years and find that instructional cost estimates of medical student education, when adjusted to a standard base year (1996 dollars), fall within a fairly narrow range: most are between $40,000 and $50,000 per student per year. Estimates of total educational resource costs show greater variation, but four of six estimates fall between approximately $72,000 and $93,000 per student per year. The authors note that present directions of curricular innovation-small-group learning, investment in information technology, and clinical education in ambulatory sites-offer little solace to those concerned with mitigating the costs of medical student education. Several proposals have been advanced to restructure medical student education in the name of efficiency and cost-effectiveness, but many are simply maneuvers to transfer responsibility for costs to other entities. Only by a net reduction of the medical school curriculum might costs truly be reduced. Yet the medical knowledge base continues to increase, as does the range of information and skills required of medical students. Unless society is prepared to change dramatically its concept of the well-educated physician, opportunities for significant reductions in the costs of medical student education are difficult to visualize.

Cost Control↗
PubMed1996

Reengineering academic medical centers: reengineering academic values?

Academic medicine is entering an era of profound, unsettling change resulting not simply from the drastic transformation of the health care marketplace but more fundamentally from the chronic, growing gap between academic medicine's seemingly insatiable demand for total resources and the supply of resources that society is willing to provide. To examine this problem, the author reviews the major factors that have shaped the development of academic medical centers (AMCs) since World War II and are now the roots of their vulnerability. The first was the major federal investment in university-based programs of science research and education that began in the 1940s; the second was the enactment in the 1960s of the Medicare/Medicaid legislation that established federal responsibility for the support of graduate medical education. After describing important characteristics (e.g., number of faculty, number of students, dollars spent on research) of the growth and accomplishment that resulted from this massive infusion of federal funds over the last few decades, the author discusses several adverse consequences, such as the de-emphasis on education in favor of research and clinical service delivery and the serious disjunction between the internal labor markets of the AMCs and the external labor markets of the real world that AMCs' graduates enter. The author then analyzes the severe challenges being faced by academic medicine in research, education, and clinical practice in the emerging resource-limited environment. Of particular concern are the fate of the clinical investigator and the future of clinical research. The author concludes with a list of four feasible strategic options for AMCs (e.g., "build one's own system") and an extensive list of what he believes AMCs will do to respond to the stresses now upon them (e.g., capitalize on unique strengths rather than trying to compete in all areas). He concludes that it will take courage for AMCs to preserve their core values in the new era, but that this can be done if AMCs craft new adaptive structures that are better attuned to the new environment and not wedded to one that is vanishing.

Academic Medical Centers↗
PubMed1996

Preserving medical schools' academic mission in a competitive marketplace.

To gain a better understanding of the effects on medical schools of transformations in medical practice, science, and public expectations, the AAMC in 1994 formed the Advisory Panel on the Mission and Organization of Medical Schools and appointed six working groups to address relevant issues. This article is a report of the findings of the Working Group on Preserving Medical Schools' Academic Mission in a Competitive Marketplace, which was charged with exploring how medical schools could acquire and/or preserve an adequate patient base for teaching, research, and income generation in a competitive marketplace. The other groups' reports will appear in future issues of Academic Medicine. To understand the diversity of approaches that schools have taken to achieve this goal and to preserve their missions, the group interviewed representatives of nine medical schools, selected to represent a cross section of U.S. medical schools. The interviews took place on four occasions between June 1995 and March 1996. The information and comments shared by participants helped the working group gain insight into the fundamental issues it had been charged to address, including those of new delivery structures, what value schools offer to delivery structures, how education and research can be incorporated and supported financially, possible new pressures on relationships between medical schools and teaching hospitals, changes in faculty physicians' employment relationships and terms, and the role of the medical school in graduate medical education. In collecting and analyzing the data, the working group focused on the distinction between protecting an institution's existing enterprise and preserving an institution's core mission. This article gives a detailed overview of the information and comments each school presented, organized under the appropriate question. The working group's conclusions and commentaries on the findings follow. An appendix presents more detailed summaries of the schools' presentations, organised as case studies. The picture that emerges is complex. The working group concluded that medical schools will take a variety of approaches to define and preserve their missions. Most, but not all, medical schools will be able to secure the patient bases necessary to fulfill their missions even in a competitive marketplace. However, the nature of many of the schools is likely to change, and it is not clear whether the core missions of education and research will continue at their present levels at all schools.

Costs and Cost Analysis↗
PubMed1996

Effects of various hygiene procedures on the surface characteristics of titanium abutments.

The use of cleaning instruments on titanium implants may cause undesired surface alterations. In a qualitative and quantitative assessment of these alterations, 5 titanium implant abutments were treated with a steel curet, a prototype pure titanium curet, an air abrasive polishing system, and an ultrasonic system. Custom-made polymer templates, used to secure the curet to a vertical guide bar and a spring scale to maintain a constant instrument pressure, guaranteed a standardized procedure and reproducible results. The ultrasonic and the air abrasive polishing method were also standardized. Evaluation by scanning electron microscopy (SEM) revealed surface alterations for all instruments and systems except the plastic curet, which did not roughen the surface at all. The confocal laser-scanning microscope allows a 3-dimensional reproduction of these surface alterations and their direct measurement. The profilometric tracing was not sensitive enough to register the minor effects caused by the titanium curet and the air abrasive polishing system. Dimensions of the resulting surface microstructure could be determined with the laser-scanning microscope. Since the influence of such surface defects on the peri-implant tissue reaction is unpredictable, the titanium curet and the air abrasive system can only be recommended with restrictions. The steel curet and the ultrasonic system proved to be totally unsuitable for cleaning titanium implants.

Curettage↗
PubMed1995

The JIM interview. David Korn, MD.

When David Korn, MD, was named dean of the Stanford University School of Medicine on October 9, 1984, he assumed leadership of a world class research institution. Stanford was at the forefront of medicine in the areas of transplantation and oncology, and the steady influx of privately insured patients had generated a net operating surplus of $17 million in that year alone. However, in the same issue of the Stanford University Hospital newsletter which announced the selection of Korn as Dean, a small article appeared on a new prospective payment system based on diagnosis-related groups (DRGs). The article stated that the new system had begun smoothly, though some payments for cost outliers had been delayed. Other cost containment measures soon followed, most notably the implementation of managed care, and by 1990, Stanford was $14 million in the red. Buffeted by changes in medical reimbursement, competition with less costly hospitals, and a nasty squabble with Congress over indirect research costs, Stanford has been on the frontlines of a struggle now confronting many academic medical centers. After successfully consolidating the university's clinical services into a unified Stanford Health System, Korn announced that he would be stepping down as Dean on April 1. Interviewed in his office in Palo Alto, Korn reflected on the difficulties of dealing with managed care, the current financial state of the institution, and what Stanford's experience may predict for other academic medical centers.

Academic Medical Centers↗
PubMed1989

Human DNA polymerase alpha: predicted functional domains and relationships with viral DNA polymerases.

The primary sequence of human DNA polymerase alpha deduced from the full-length cDNA contains regions of striking similarity to sequences in replicative DNA polymerases from Escherichia coli phages PRD1 and T4, Bacillus phage phi 19, yeast DNA polymerase I, yeast linear plasmid pGKL1, maize S1 mitochondrial DNA, herpes family viruses, vaccinia virus, and adenovirus. The conservation of these homologous regions across this vast phylogenetic expanse indicates that these prokaryotic and eukaryotic DNA polymerases may all have evolved from a common primordial gene. Based on the sequence analysis and genetic results from yeast and herpes simplex virus studies, these consensus sequences are suggested to define potential sites that subserve essential roles in the DNA polymerase reaction. Two of these conserved regions appear to participate directly in the active site required for substrate deoxynucleotide interaction. One region toward the carboxyl-terminus has the potential to be the DNA interacting domain, whereas a potential DNA primase interaction domain is predicted toward the amino-terminus. The provisional assignment of these domains can be used to identify unique or dissimilar features of functionally homologous catalytic sites in viral DNA polymerases of pathogenetic significance and thereby serve to guide more rational antiviral drug design.

Amino Acid Sequence↗
PubMed1988

The evolutionary conservation of DNA polymerase alpha.

The evolutionary conservation of DNA polymerase alpha was assessed by immunological and molecular genetic approaches. Four anti-human KB cell DNA polymerase alpha monoclonal antibodies were tested for their ability to recognize a phylogenetically broad array of eukaryotic DNA polymerases. While the single non-neutralizing antibody used in this study recognizes higher mammalian (human, simian, canine, and bovine) polymerases only, three neutralizing antibodies exhibit greater, but variable, extents of cross-reactivity among vertebrate species. The most highly cross-reactive antibody recognizes a unique epitope on a 165-180 kDa catalytic polypeptide in cell lysates from several eukaryotic sources, as distant from man as the amphibians. Genomic Southern hybridization studies with the cDNA of the human DNA polymerase alpha catalytic polypeptide identify the existence of many consensus DNA sequences within the DNA polymerase genes of vertebrate, invertebrate, plant and unicellular organisms. These findings illustrate the differential evolutionary conservation of four unique epitopes on DNA polymerase alpha among vertebrates and the conservation of specific genetic sequences, presumably reflective of critical functional domains, in the DNA polymerase genes from a broad diversity of living forms.

Animals↗
PubMed1988

Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases.

We have isolated cDNA clones encoding the human DNA polymerase alpha catalytic polypeptide. Studies of the human DNA polymerase alpha steady-state mRNA levels in quiescent cells stimulated to proliferate, or normal cells compared to transformed cells, demonstrate that the polymerase alpha mRNA, like its enzymatic activity and de novo protein synthesis, positively correlates with cell proliferation and transformation. Analysis of the deduced 1462-amino-acid sequence reveals six regions of striking similarity to yeast DNA polymerase I and DNA polymerases of bacteriophages T4 and phi 29, herpes family viruses, vaccinia virus and adenovirus. Three of these conserved regions appear to comprise the functional active site required for deoxynucleotide interaction. Two putative DNA interacting domains are also identified.

Amino Acid Sequence↗
PubMed1988

Gene expression of human DNA polymerase alpha during cell proliferation and the cell cycle.

We studied the expression of the human DNA polymerase alpha gene during cell proliferation, during cell progression through the cell cycle, and in transformed cells compared with normal cells. During the activation of quiescent cells (G0 phase) to proliferate (G1/S phases), the steady-state mRNA levels, rate of synthesis of nascent polymerase protein, and enzymatic activity in vitro exhibited a substantial and concordant increase prior to the peak of in vivo DNA synthesis. In transformed cells, the respective values were amplified greater than 10-fold. In actively growing cells separated into discrete stages of the cell cycle by counterflow elutriation or by mitotic shakeoff, levels of steady-state transcripts, translation rates, and enzymatic activities of polymerase alpha were constitutively and concordantly expressed at all stages of the cell cycle, with only a moderate elevation prior to the S phase and a slight decline in the G2 phase. These findings support the conclusion that the regulation of human DNA polymerase alpha gene expression is at the transcriptional level and strongly suggest that the regulatory mechanisms that are operative during the entrance of a cell into the mitotic cycle are fundamentally different from those that modulate polymerase alpha expression in continuously cycling cells.

Cell Cycle↗
PubMed1986

Structural and enzymological characterization of immunoaffinity-purified DNA polymerase alpha.DNA primase complex from KB cells.

We describe the polypeptide structure and some of the catalytic properties of a DNA polymerase alpha.DNA primase complex that can be prepared from KB cells by immunoaffinity purification. The procedure is based on monoclonal antibodies that were raised against a biochemically purified, catalytically active core protomer of the polymerase. In all respects tested, the basic mechanism of substrate recognition and binding by the immunoaffinity-purified polymerase is qualitatively identical to that of the core protomer. The immunoaffinity-purified KB cell polymerase alpha X DNA primase is structurally complex. On the basis of extensive immunochemical analyses with five independent monoclonal antibodies, three of which are potent neutralizers of polymerase alpha activity, peptide mapping studies, and the application of a sensitive immunoassay that permits detection of polymerase alpha antigens in crude cell lysates, we have established that the principal form of catalytically active DNA polymerase alpha in KB cells is a phosphoprotein with a molecular mass of 180 kilodaltons. This protein is stable in vivo, with an estimated half-life of greater than or equal to 15 h. In contrast, the polypeptide is extremely fragile in vitro and generates partial degradation products of p165, p140, and p125 that explain the "microheterogeneity" typically exhibited by polymerase alpha peptides in denaturing polyacrylamide gels. In addition to the catalytically active polymerase alpha polypeptide(s), the immunopurified enzyme fraction typically contains three other proteins, p77, p55, and p49, the functions of which have not yet been established. These proteins do not display polymerase alpha epitopes and have been shown by peptide mapping to be independent species that are unrelated either to the large polymerase peptides or to one another. The polypeptide p77 is also a phosphoprotein, and in both p180 and p77 the phosphorylated amino acids are exclusively serine and threonine.

Antibodies, Monoclonal↗