Search PubMed⌕ Search

Biomedical subjects

Jaimo Ahn

Publications and source records attributed to Jaimo Ahn.

12 recordsLinked to original sources
PubMed2006

The required research rotation in residency: the University of Pennsylvania experience, 1978-1993.

The University of Pennsylvania orthopaedic surgery residency program under the direction of Dr. Carl T. Brighton was uniquely structured to require a year of research as part of a 5-year program. This requirement was instituted to foster critical thinking, and not necessarily to produce academic orthopaedic surgeons. Nonetheless, measures of academic productivity of the 127 residents who trained under Dr. Brighton's leadership may be instructive. The purpose of this study was to assess metrics of academic productivity. In addition, the six current and former chairmen of orthopaedic surgery programs who performed research while residents at the University of Pennsylvania were surveyed for their impressions regarding required research rotations. Fifty-nine percent of the University of Pennsylvania residents took faculty positions after training; 75% published a peer-reviewed paper after residency; and 17% are current members of the American Orthopaedic Association. Overall, the chairmen surveyed found great value in their own resident research experience, but none have replicated the Brighton model of residency organization. Only two of the six programs have a research year: at both, this research rotation is in addition to the standard 5 years of clinical education and only at one are all residents required to participate.

Authorship↗
PubMed2006

Dysregulation of the BMP-4 signaling pathway in fibrodysplasia ossificans progressiva.

Identification of gene mutations in Mendelian disorders is often determined by linkage analysis and positional cloning, an approach that is difficult for fibrodysplasia ossificans progressiva (FOP) due to a low reproductive fitness that results in a small number of multigenerational families showing inheritance of the disease. Altered signaling pathways can be investigated as a complementary method to identify the consequences of the mutated gene responsible for FOP and to identify potential therapeutic targets. Candidate signaling pathways for FOP are those that malfunctioning could account for the malformation of the great toes during embryonic development and could explain the postnatal progressive heterotopic endochondral ossification. Signaling pathways that fit these criteria are the BMP signaling pathway and its interacting pathways. A large body of data suggest that the BMP-4 signaling pathway is dysregulated in FOP.

Animals↗
PubMed2005

Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA.

UNLABELLED: FOP is a disorder in which skeletal muscle is progressively replaced with bone. FOP lymphocytes, a model system for exploring the BMP pathway in these patients, exhibit a defect in BMPRIA internalization and increased activation of downstream signaling, suggesting that altered BMP receptor trafficking underlies ectopic bone formation in this disease. INTRODUCTION: Fibrodysplasia ossificans progressiva (FOP) is a severely disabling disorder characterized by progressive heterotopic ossification of connective tissues. Whereas the genetic defect and pathophysiology of this condition remain enigmatic, BMP4 mRNA and protein are overexpressed, and mRNAs for a subset of secreted BMP antagonists are not synthesized at appropriate levels in cultured lymphocytes from FOP patients. These data suggest involvement of altered BMP signaling in the disease. In this study, we investigate whether the abnormality is associated with defective BMP receptor function in lymphocytes. MATERIALS AND METHODS: Cell surface proteins were quantified by fluorescence-activated cell sorting (FACS). Protein phosphorylation was assayed by immunoprecipitation and immunoblotting. Protein synthesis and degradation were examined by [35S]methionine labeling and pulse-chase assays. mRNA was detected by RT-PCR. RESULTS: FOP lymphocytes expressed 6-fold higher levels of BMP receptor type IA (BMPRIA) on the cell surface compared with control cells and displayed a marked reduction in ligand-stimulated internalization and degradation of BMPRIA. Moreover, in control cells, BMP4 treatment increased BMPRIA phosphorylation, whereas BMPRIA showed ligand-insensitive constitutive phosphorylation in FOP cells. Our data additionally support that the p38 mitogen-activated protein kinase (MAPK) signaling pathway is a major BMP signaling pathway in these cell lines and that expression of inhibitor of DNA binding and differentiation 1 (ID-1), a transcriptional target of BMP signaling, is enhanced in FOP cells. CONCLUSIONS: These data extend our previous observations of misregulated BMP4 signaling in FOP lymphocytes and show that cell surface overabundance and constitutive phosphorylation of BMPRIA are associated with a defect in receptor internalization. Altered BMP receptor trafficking may play a significant role in FOP pathogenesis.

Bone Morphogenetic Protein 4↗
PubMed2005

Educational views and attitudes, and career goals of MD-PhD students at the University of Pennsylvania School of Medicine.

PURPOSE: Despite the documented contribution of graduates of MD-PhD programs to the medical profession, few data exist concerning the views, attitudes, and career goals of students before they graduate from such programs. METHOD: All 167 students enrolled in the University of Pennsylvania School of Medicine Combined Degree Program in the spring of 2002 were invited to participate in an IRB-approved online questionnaire consisting of 81 multiple-choice questions covering students' demographics, satisfaction with their educational experience, future goals and career aspirations, and attitudes and views concerning the physician-scientist model. RESULTS: The 96 MD-PhD students (57.5%) who completed the questionnaire represented a diverse group with individuals from every stage of training. The majority of students were satisfied with their overall educational experience (90.5%). Although students reported an interest in a wide range of clinical specialties, 84.4% indicated plans to pursue a career in research and 79.2% preferred a position at an academic medical center. However, a larger percentage of males (70.7%) than females (50.0%) listed research as their primary professional activity. The range of students' views and attitudes regarding the physician-scientist model suggests that additional education and discussion are warranted. CONCLUSION: The MD-PhD students surveyed at the University of Pennsylvania were satisfied with their education and most were planning research-oriented careers. Yet, the aspirations, views and concerns of individual MD-PhD students were varied. The authors believe this information in aggregate will prove useful to current and future students, combined degree programs, policymakers, and residency directors.

Adult↗
PubMed2004

MD-PhD students in a major training program show strong interest in becoming surgeon-scientists.

A wide spectrum of individuals have discussed the importance of promoting research in orthopaedics and of developing clinician-scientists (physicians who also do significant research) in the field. Although orthopaedic research may benefit from recruitment of MD-PhD students as clinician-scientists, it is unclear to what extent MD-PhD students are interested in pursuing research and surgical specialties concurrently. To better understand their professional goals, all MD-PhD students enrolled in our institution's training program were invited to complete an online questionnaire concerning training satisfaction and future career goals. Twenty-four percent of respondents (57.5% response rate of 167 recruits) reported a primary clinical interest in a surgical field (3% interest in orthopaedics); interest was strongest late in training. The majority of surgical MD-PhD students, like nonsurgical students, were planning to make research a significant part of their careers. In addition, students identified the importance of factors such as family issues and faculty role models in determining their clinical interests. The study data indicate that MD-PhD students have strong interests in becoming surgical clinician-scientists. They also suggested that active recruitment (especially early in training) that is responsive to the personal and professional needs of students has the potential to increase the number of clinician-scientists in orthopaedics.

Adult↗
PubMed2003

Exoneration of NF-kappaB dysregulation in fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva is a disabling genetic disorder characterized by congenital skeletal malformations and progressive heterotopic ossification. New episodes of ossification are heralded by preosseous inflammatory lesions replete with B and T lymphocytes that overexpress bone morphogenetic protein-4. NF-kappaB is an inflammatory mediator that plays a critical role in developmental skeletogenesis and in suppression of bone morphogenetic protein-4 expression. Because of its multiple roles in inflammation, skeletogenesis, and bone morphogenetic protein-4 regulation, NF-kappaB may play an important functional role in the pathogenesis of fibrodysplasia ossificans progressiva. To clarify the potential role of NF-kappaB in the pathophysiologic features of fibrodysplasia ossificans progressiva, the role of NF-kappaB in regulating bone morphogenetic protein-4 signaling in patient-derived lymphoblastoid cell lines was examined. General NF-kappaB activity and specific NF-kappaB suppression of bone morphogenetic protein-4 expression were not altered in fibrodysplasia ossificans progressiva. In addition, despite the proximity of the gene for the p50 subunit of NF-kappaB (NFKB1 on long arm of chromosome 4) to the recently mapped locus for fibrodysplasia ossificans progressiva, a detailed linkage exclusion analysis in four multigenerational families with the disorder excluded NFKB1 as the causative gene for fibrodysplasia ossificans progressiva. These data exonerate NF-kappaB as the critical molecular and genetic pathogenic mediator in fibrodysplasia ossificans progressiva and, therefore, implicate a defect in another regulatory pathway as the cause for bone morphogenetic protein-4 overexpression in the disease.

Alleles↗
PubMed2003

Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis.

BACKGROUND: Fibrodysplasia ossificans progressiva is a rare genetic disorder characterized by congenital malformations of the great toes and by progressive heterotopic bone formation. Bone morphogenetic protein-4 (BMP-4) messenger ribonucleic acid (mRNA) and protein are uniquely overexpressed in lymphocytes and lesional cells from patients who have fibrodysplasia ossificans progressiva. However, the BMP-4 gene is not mutated in fibrodysplasia ossificans progressiva. The activities of BMPs are specified in part by the formation of morphogen gradients that are further regulated by an array of secreted antagonists. Recent studies have indicated that BMP-4 upregulates the expression of the BMP antagonists noggin, gremlin, and follistatin, thereby establishing an autoregulatory feedback loop. Therefore, a defect in the feedback pathway between BMP-4 and one or more of its extracellular antagonists could contribute to the elevated BMP-4 activity characteristic of fibrodysplasia ossificans progressiva. METHODS: Basal and BMP-4-induced expression of noggin, gremlin, follistatin, and chordin mRNA were investigated in control and fibrodysplasia ossificans progressiva lymphoblastoid cell lines with use of reverse transcriptase-polymerase chain reaction and Northern analysis. RESULTS: In the absence of exogenous BMP-4 stimulation (basal state), steady-state levels of all of the BMP antagonists that were investigated were similar in fibrodysplasia ossificans progressiva and control cell lines. Upon stimulation with recombinant human BMP-4, control lymphoblastoid cell lines exhibited a marked increase in expression of noggin and gremlin mRNA. Fibrodysplasia ossificans progressiva cells, however, showed a dramatically attenuated response to BMP-4 stimulation compared with that of controls. CONCLUSIONS: These data indicate a paresis of a BMP-antagonist response, suggesting the loss of a negative feedback mechanism by which cells normally regulate the magnitude and boundaries of ambient morphogenetic signals. This paresis may account in part for the increased BMP-4 activity in fibrodysplasia ossificans progressiva.

Bone Morphogenetic Protein 4↗
PubMed2002

Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia.

BACKGROUND: Progressive osseous heteroplasia (POH), an autosomal dominant disorder, is characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue. Occasional reports of mild heterotopic ossification in Albright's hereditary osteodystrophy (AHO) and a recent report of two patients with AHO who had atypically extensive heterotopic ossification suggested a common genetic basis for the two disorders. AHO is caused by heterozygous inactivating mutations in the GNAS1 gene that result in decreased expression or function of the alpha subunit of the stimulatory G protein (Gsalpha) of adenylyl cyclase. METHODS: We tested the hypothesis that GNAS1 mutations cause POH, using the polymerase chain reaction to amplify GNAS1 exons and exon-intron boundaries in 18 patients with sporadic or familial POH. RESULTS: Heterozygous inactivating GNAS1 mutations were identified in 13 of the 18 probands with POH. The defective allele in POH is inherited exclusively from fathers, a result consistent with a model of imprinting for GNAS1. Direct evidence that the same mutation can cause either POH or AHO was observed within a single family, in which the phenotype correlated with the parental origin of the mutant allele. CONCLUSIONS: Paternally inherited inactivating GNAS1 mutations cause POH. This finding extends the range of phenotypes derived from haplo insufficiency of GNAS1, provides evidence that imprinting is a regulatory mechanism for GNAS1 expression, and suggests that Gsalpha is a critical negative regulator of osteogenic commitment in nonosseous connective tissues.

Base Sequence↗