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Biomedical subjects

W N Kelley

Publications and source records attributed to W N Kelley.

At least 19 recordsLinked to original sources
PubMed2001

Blueprint for discovery in academic medicine: plans, process and outcomes.

By the end of the decade, we had fully implemented most of the recommendations of the Molinoff Report. Our programmatic analysis is summarized in Table 11. While the space needs identified in the Molinoff Report were met by BRB I, II, and III (289,000 nsf as compared [table: see text] to 276,000 nsf as planned), it was possible to provide additional, somewhat unanticipated, research space (111,000 nsf) prior to the end of the decade. The faculty has now developed a research plan for the next decade. It is also important to emphasize that the total faculty grew by 41% [table: see text] over the decade and most of that growth occurred with faculty spending a substantial part of their time in clinical practice. Hence, the dramatic improvement in research funding of over 200% was due largely to the enhanced productivity of our faculty. By taking an organized planning approach deeply seated in the faculty, consistent with Trustee directives and with measurable outcomes, we were successful in growing the research programs within the School of Medicine of the University of Pennsylvania. We believe this particular approach, taken with a focus on multidisciplinary research, [table: see text] was the right one for the 1990s. In the final analysis, it is abundantly clear that outstanding faculty, working in an exciting supportive environment, was the most important factor for success. We are not certain what the right approach will be for the future. Clearly, with the important advances in genomics and information technology, the importance of the team, even if a virtual one world-wide, cannot be overstated. While research is only one mission of the School of Medicine, clearly, our visible success in research played an important role in the overall improvement in the School of Medicine as measured by others. For example, the ranking of the School of Medicine by U.S. News & World Report, perhaps the most widely used ranking by the lay press, went from 10th to 3rd behind only Harvard and Johns Hopkins during the period of the 90s (Table 12).

Academic Medical Centers↗
PubMed1996

Gene therapy: socioeconomic and ethical issues. A roundtable discussion.

Gene therapy research has the potential to revolutionize the way in which many human diseases are treated. Despite its enormous potential, roundtable panelists concluded that the field needs time to mature scientifically without pressure to develop a marketable therapeutic product. In addition, health care decision makers, physicians, and the lay public need to be educated on the future medical, economic, and ethical ramifications of gene therapy.

Clinical Trials as Topic↗
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

Capturing the promise of science in medical schools.

To gain a better understanding of the effects on medical schools of transformations in medical practice, science, and public expectations, the Association of American Medical Colleges (AAMC) constituted the Advisory Panel on the Mission and Organization of Medical Schools (APMOMS) in 1994. APMOMS created six working groups to address the issues deemed by panel members to be of highest priority. This article is a report of the findings of the Working Group on Capturing the Promise of Medical Research, which addressed questions concerning the direction of research and the integration of scientific developments in medical education and practice. The working group explored a broad panorama of issues, including those related to sustaining the accomplishments, momentum, and progress of medical research. A dominant theme emerged: the central importance of an environment of discovery to the core missions of medical schools. The present article consists of the group's comments and recommendations on the main topic-the promise of biomedical research in relation to medical education-and their comments and recommendations on five other topics that have important relationships to the main topic and to the group's central charge. These are ethics; academia-industry relations; the administrative structure of medical schools; university-medical school relations; and research funding.

Diffusion of Innovation↗
PubMed1992

Faculty tracks and academic success.

In 1977, the Department of Internal Medicine at the University of Michigan implemented two specific faculty career tracks, the physician-scientist and clinician-scholar, to define more clearly the goals and expectations to which individuals should strive to achieve academic success. In response to the changing environment, a leadership track and a full-time clinical track were added. Although concerns about comparability, transfer between tracks, and research productivity were raised initially, they were alleviated as it became apparent that the ability to achieve tenure was similar in the physician-scientist and clinician-scholar tracks. The development of well-defined faculty tracks has facilitated the alignment of talents, training, and effort with career goals. It has also enabled us to protect the time of young investigators to pursue their research activities and to define the expectations for promotion for clinicians with a major commitment to patient care.

Administrative Personnel↗
PubMed1991

Determination of the mutations responsible for the Lesch-Nyhan syndrome in 17 subjects.

Hypoxanthine--guanine phosphoribosyltransferase (HPRT) is a purine salvage enzyme that catalyzes the conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. Previous studies of mutant HPRT proteins analyzed at the molecular level have shown a significant heterogeneity. This investigation further verifies this heterogeneity and identifies insertions, deletions, and point mutations. The direct sequencing of the polymerase chain reaction-amplified product of reverse-transcribed HPRT mRNA enabled the rapid identification of the mutations found in 17 previously uncharacterized cell lines derived from patients with the Lesch-Nyhan syndrome.

Cell Line↗
PubMed1991

A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects.

Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disorder which causes 2,8-dihydroxy-adenine urolithiasis. The estimated incidence of heterozygosity in Caucasian and Japanese populations is 1%. Mutant alleles responsible for the disease have been classified as APRT*Q0 (type I) and APRT* (type II). In our previous study, we demonstrated in APRT*J a single common base change which accounts for 70% of the Japanese mutants. The present report describes the analysis of an APRT*Q0 mutation in Japanese subjects. Two nucleotide substitutions common to all seven affected alleles from four unrelated subjects (three homozygotes and a heterozygote) were identified: G----A at nucleotide position 1453 and C----T at 1456. The G----A altered the amino acid Trp98 to a stop codon. The C----T did not alter Ala99. These point mutations were demonstrated by sequence analysis of polymerase chain reaction (PCR)-amplified genomic DNA and cDNA. The G----A change at 1453 results in the elimination of a PflMI site in the APRT gene. PflMI digests, which were used to confirm the G----A transition, can be useful in screening for this specific mutation.

Adenine Phosphoribosyltransferase↗
PubMed1991

Identification of 17 independent mutations responsible for human hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency.

Complete hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency causes the Lesch-Nyhan syndrome, an X-linked, purine metabolism disorder manifested by hyperuricemia, hyperuricaciduria, and neurologic dysfunction. Partial HPRT deficiency causes hyperuricemia and gout. One requirement for understanding the molecular basis of HPRT deficiency is the determination of which amino acids in this salvage enzyme are necessary for structural or catalytic competence. In this study we have used the PCR coupled with direct sequencing to determine the nucleotide and subsequent amino acid changes in 22 subjects representing 17 unrelated kindreds from the United Kingdom. These mutations were confirmed by using either RNase mapping or Southern analyses. In addition, experiments were done to determine enzyme activity and electrophoretic mobility, and predictive paradigms were used to study the impact of these amino acid substitutions on secondary structure.

Chromosome Deletion↗
PubMed1989

The integrated inpatient management model. A new approach to clinical practice.

The delivery and financing of health care have undergone a metamorphosis over the past 10 years. These changes have been particularly dramatic for hospital care. The new health care environment, with more prospective-payment and managed-care systems and less fee-for-service payment for both physicians and hospitals, has made physicians and hospitals mutually dependent. A hospital's long-term financial viability is now dependent largely on the practice style of its physicians. The Department of Internal Medicine at The University of Michigan has developed a new clinical management system called the Integrated Inpatient Management Model (IIMM). This new system includes a major revision of the hospital organization structure, new administrative information systems, and new clinical information systems. Physicians in the Department of Internal Medicine have assumed for the first time formal organizational responsibility for many aspects of the operations of the inpatient medical service. The IIMM represents a prototype of a system that we believe offers considerable promise for involving physicians to a much greater extent in the management of the nation's hospitals. We hope that describing the system in detail will facilitate the development of other systems for the management of the inpatient practice of internal medicine.

Diagnosis-Related Groups↗
PubMed1989

Expression of human HPRT mRNA in brains of mice infected with a recombinant herpes simplex virus-1 vector.

Complete deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) results in a devastating neurological disease, the Lesch-Nyhan syndrome. This disorder has been identified as a candidate for initial attempts at somatic cell gene therapy. We have previously reported the construction of a recombinant herpes simplex virus type 1 (HSV-1) vector containing human hprt cDNA sequences under the regulatory control of the viral thymidine kinase gene (tk) [Palella et al., Mol. Cell. Biol. 8 (1988) 457-460]. Infection of HPRT- cultured rat neuronal cells with these vectors resulted in transient expression of human hprt. In this paper, we report the expression of human hprt mRNA transcripts in the brains of mice infected in vivo with this vector by direct intracranial inoculation. Human hprt transcripts were distinguished from endogenous mouse transcripts by RNase A mapping using riboprobes transcribed from human hprt cDNA. These initial studies demonstrate the transfer and transcription of a human gene in brain cells by direct in vivo infection with recombinant HSV-1 vectors.

Animals↗
PubMed1989

Human hypoxanthine-guanine phosphoribosyltransferase deficiency. The molecular defect in a patient with gout (HPRTAshville).

The genetic basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency has been identified by nucleotide sequence analysis of HPRT cDNAs cloned from a patient with gout. A single nucleotide change was identified in two independent clones: an A to G transition at nucleotide 602. Confirmation of a mutation at this site was provided by RNase mapping analysis. The predicted consequence of this transition is an aspartic acid to glycine substitution at amino acid 201. We have designated this variant HPRTAshville. Prior to this report, enzyme activity in HPRTAshville had not been detected by routine assay. Using more sensitive techniques, including an in situ gel assay for HPRT activity, we were able to demonstrate electrophoretic, kinetic, and structural differences between HPRTAshville and normal HPRT. Electrophoretic migration of HPRTAshville has elevated Michaelis constants for 5-phosphoribosyl-1-pyrophosphate and hypoxanthine. Predicted secondary structural alterations may result from the aspartic acid to glycine substitution.

Amino Acid Sequence↗
PubMed1989

Lesch-Nyhan syndrome due to a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale).

We have cloned and sequenced a full length cDNA for HPRT cDNA for HPRTYale isolated from Lesch-Nyhan subject and identified a single nucleotide substitution which results in amino acid substitution of glycine to arginine. Since most HPRT mutants have normal levels of specific HPRT messenger RNA, mutant cDNA analysis is the method of choice to define the mutation in HPRT deficient subjects.

Amino Acid Sequence↗