An admission model for medical schools.

Complex societal issues affect medical education and thus require new approaches from medical school admission officers. One of these issues--the recognition that the attributes of good doctors include character qualities such as compassion, altruism, respect, and integrity--has resulted in the recent focus on the greater use of qualitative variables, such as those just stated, for selected candidates. In addition, more emphasis is now being placed on teaching and licensure testing of the attributes of the profession during the four-year curriculum. The second and more contentious issue concerns the system used to admit white and minority applicants. Emphasizing character qualities of physicians in the admission criteria and selection process involves a paradigm shift that could serve to resolve both issues. To make this or any paradigm shift in admission policy, medical schools must think about all the elements of admission and their interrelationships. A model of medical school admission is proposed that can provide understanding of the admission system and serve as a heuristic guide. This model consists of (1) the applicant pool; (2) criteria for selection; (3) the admission committee; (4) selection processes and policies; and (5) outcomes. Each of these dimensions and the interrelationships among the dimensions are described. Finally, a hypothetical example is provided in which the model is used to help a medical school change its admission process to accommodate a new emphasis in the school's mission.

ICAM-1-induced expression of proinflammatory cytokines in astrocytes: involvement of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways.

ICAM-1 is a transmembrane glycoprotein of the Ig superfamily involved in cell adhesion. ICAM-1 is aberrantly expressed by astrocytes in CNS pathologies such as multiple sclerosis, experimental allergic encephalomyelitis, and Alzheimer's disease, suggesting a possible role for ICAM-1 in these disorders. ICAM-1 has been shown to be important for leukocyte diapedesis through brain microvessels and subsequent binding to astrocytes. However, other functional roles for ICAM-1 expression on astrocytes have not been well elucidated. Therefore, we investigated the intracellular signals generated upon ICAM-1 engagement on astrocytes. ICAM-1 ligation by a mAb to rat ICAM-1 induced mRNA expression of proinflammatory cytokines such as IL-1alpha, IL-1beta, IL-6, and TNF-alpha. Examination of cytokine protein production revealed that ICAM-1 ligation results in IL-6 secretion by astrocytes, whereas IL-1beta and IL-1alpha protein is expressed intracellularly in astrocytes. The involvement of mitogen-activated protein kinases (MAPKs) in ICAM-1-mediated cytokine expression in astrocytes was tested, as the MAPK extracellular signal-regulated kinase (ERK) was previously shown to be activated upon ICAM-1 engagement. Our results indicate that ERK1/ERK2, as well as p38 MAPK, are activated upon ligation of ICAM-1. Studies using pharmacological inhibitors demonstrate that both p38 MAPK and ERK1/2 are involved in ICAM-1-induced IL-6 expression, whereas only ERK1/2 is important for IL-1alpha and IL-1beta expression. Our data support the role of ICAM-1 on astrocytes as an inflammatory mediator in the CNS and also uncover a novel signal transduction pathway through p38 MAPK upon ICAM-1 ligation.

Oncostatin M regulation of interleukin-6 expression in astrocytes: biphasic regulation involving the mitogen-activated protein kinases ERK1/2 and p38.

Oncostatin M (OSM) is a member of the interleukin (IL)-6 family of cytokines and has both pro- and anti-inflammatory properties. Of interest, OSM has functional effects within the CNS. We have shown recently that OSM can modulate expression of the cytokine IL-6 in astrocytes. Herein we characterize the molecular mechanisms and signaling cascades involved in this response. OSM induces IL-6 protein expression in a dose- and time-dependent manner in astrocytes. In addition, OSM can synergize with the cytokines tumor necrosis factor-alpha, IL-1beta, and transforming growth factor-beta for enhanced IL-6 expression. Using neutralizing antibodies to gp 130, the OSM receptor (OSMR), and the leukemia inhibitory factor receptor (LIFR), we document that OSM exclusively uses the OSMR/gp 130 heterodimer in signaling events, rather than the LIFR/gp 130 heterodimer. Kinetic analysis of OSM-induced IL-6 mRNA reveals two up-regulatory events. The first, peaking at 1 h, is transient, does not require protein synthesis, and is regulated at the transcriptional level. The second, peaking between 6 and 8 h, is prolonged and sensitive to puromycin, suggesting a requirement for de novo protein synthesis, and also is transcriptionally regulated. OSM-induced IL-6 mRNA and protein expression is inhibited by the mitogen-activated protein kinase (MAPK) inhibitors U0126 and SB202190, suggesting a requirement for the MAPKs ERK1/2 and p38 in this response. Finally, we show that the MAPKs ERK1/2 and p38 are activated by OSM in astrocytes and that this activation is reduced by the MAPK inhibitors. These data demonstrate that OSM induces IL-6 expression in astrocytes and that the MAPKs ERK1/2 and p38 participate in this response.

Interleukin-6 (IL-6) production by astrocytes: autocrine regulation by IL-6 and the soluble IL-6 receptor.

In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-alpha or IL-1beta on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-alpha or IL-1beta plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-alpha- or IL-1beta-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-alpha or IL-1beta plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-alpha for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-alpha and IL-1beta.

Program directors' responses to a survey on variables used to select residents in a time of change.

PURPOSE: In an effort to gain information to give to students seeking to optimize their chances of attaining residency positions, the authors assessed actual and projected changes in the process to select residents and determined the relative weights that program directors assigned to academic and personal criteria. METHOD: In the fall of 1996, the authors mailed questionnaires to 1,200 program directors in 14 specialties requesting responses in four categories: current and projected changes in programs, current experiences with applicants and residents, the residency selection process, and the interview. RESULTS: Of those program directors, 794 (66.2%) responded. Nearly twice as many directors in university-based hospitals projected decreases in residency positions over the next five years as did directors in university-affiliated hospitals. A significant percentage of specialties expected increased competition for positions. The authors observed a tight clustering of highly valued academic variables in the most competitive group of specialties. Some specialties admitted to using a first-come, first-served basis for selecting candidates for interview. CONCLUSIONS: The study found significant changes in the process to select residents, including a decrease in residency positions, a continuation of this decrease, and a protracted escalation of competition for positions.

Interleukin-6 expression and regulation in astrocytes.

The physiological function of interleukin-6 (IL-6) within the central nervous system (CNS) is complex; IL-6 exerts neurotrophic and neuroprotective effects, and yet can also function as a mediator of inflammation, demyelination, and astrogliosis, depending on the cellular context. In the normal brain, IL-6 levels remain low. However, elevated expression occurs in injury, infection, stroke, and inflammation. Given the diverse biological functions of IL-6 and its expression in numerous CNS conditions, it is critical to understand its regulation in the brain in order to control its expression and ultimately its effects. Accumulating data demonstrate that the predominant CNS source of IL-6 is the activated astrocyte. Furthermore, a wide range of factors have been demonstrated to be involved in IL-6 regulation by astrocytes. In this review, we summarize information concerning IL-6 regulation in astrocytes, focusing on the role of proinflammatory factors, neurotransmitters, and second messengers.

Role of IL-6 and the soluble IL-6 receptor in inhibition of VCAM-1 gene expression.

Adhesion molecules such as VCAM-1 and ICAM-1 are increased in the central nervous system (CNS) during inflammatory responses and contribute to extravasation of leukocytes across the blood-brain barrier (BBB) and into CNS parenchyma. Astrocytes contribute to the structural integrity of the BBB and can be induced to express VCAM-1 and ICAM-1 in response to cytokines such as TNF-alpha, IL-1beta, and IFN-gamma. In this study, we investigated the influence of IL-6 on astroglial adhesion molecule expression. IL-6, the soluble form of the IL-6R (sIL-6R), or both IL-6 plus sIL-6R, had no effect on VCAM-1 or ICAM-1 gene expression. Interestingly, the IL-6/sIL-6R complex inhibited TNF-alpha-induced VCAM-1 gene expression but did not affect TNF-alpha-induced ICAM-1 expression. The inhibitory effect of IL-6/sIL-6R complex was reversed by the inclusion of anti-IL-6R and gp130 Abs, demonstrating the specificity of the response. A highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide, which is designated H-IL-6, also inhibited TNF-alpha-induced VCAM-1 expression. sIL-6R alone was an effective inhibitor of TNF-alpha-induced VCAM-1 due to endogenous IL-6 production. These results indicate that the IL-6 system has an unexpected negative effect on adhesion molecule expression in glial cells and may function as an immunosuppressive cytokine within the CNS.

Kinase inhibitors abrogate IFN-gamma-induced class II transactivator and class II MHC gene expression in astroglioma cell lines.

Multiple kinase events, involving both tyrosine (tyr) kinase and serine/threonine (ser/thr) kinase activity, are required for IFN-gamma-induced class II MHC mRNA and protein expression in primary rat astrocytes. In this study, we examined the necessity of ser/thr and tyr kinase activity for IFN-gamma-induced stimulation of class II MHC gene expression in the human astroglioma cell lines CRT and CH235, as well as the involvement of these kinases in IFN-gamma-induced expression of the class II transactivator (CIITA), a protein critical for IFN-gamma-induced transcription of class II MHC genes. We show that general ser/thr kinase inhibitors, inhibitors of the ser/thr kinase mitogen-activated protein kinase (MAPK), and tyr kinase inhibitors reduce IFN-gamma-induced class II MHC mRNA and protein expression in a dose-dependent manner. As well, these inhibitors abrogate IFN-gamma-induced CIITA mRNA expression in the astroglioma cell lines. We have further demonstrated that cells constitutively expressing the CIITA protein (2fTGH.CIITA) show no decrease in CIITA or class II MHC mRNA expression in the presence of ser/thr and tyr kinase inhibitors. Collectively, these data indicate that ser/thr kinase activity, possibly MAPK, and tyr kinase activity are required for IFN-gamma-induced expression of CIITA mRNA, and the subsequent expression of class II MHC genes.

Recommendations for changing the residency selection process based on a survey of program directors.

The authors conducted a nationwide survey of program directors participating in the 1990-91 National Resident Matching Program (NRMP) in order to solicit the directors' responses to elements of the current residency selection process and to suggested revisions. Of 680 randomly selected directors, 469 (69%) responded to the survey questionnaire, using a five-point scale, from 1, indicating strong agreement, to 5, indicating strong disagreement. The directors agreed that the senior year was distorted by the selection process, that students were pressured into making early career decisions, and that there needed to be more structure to the senior year. The directors were also in agreement that interviews, the NRMP, and the uniform notification date were working well. But deans' letters, other letters of recommendation, the Universal Application, and appointment of unmatched students were considered to be in need of improvement. The development of a centralized residency application service with the electronic transmission of data received the directors' support. The authors recommend that a task force be convened to consider changes that would improve the selection process and would reduce disruption of the students' senior year of medical education.

A new approach to standardizing the dean's letter.

Eighty-one residency program directors were surveyed to determine whether a standardized "dean's evaluation" form submitted by deans of student affairs on behalf of senior medical students would suffice in conveying information desired for the residency selection process. Program directors were asked to rate each subpart of this suggested form and to state whether the overall document was sufficiently comprehensive to serve in lieu of the deans' letters now being provided by U.S. medical schools. An overwhelming majority (83%) felt that this alternative form would be sufficient when combined with an academic transcript.

High school students' motivations for a career as a physician.

Ask achievement-oriented high school students what they think of becoming a physician and they will respond that it is not their top career choice. Of the 180 high-achieving students surveyed by the authors in 1986, 93% of the white students and 82% of the black students aspired to graduate and professional degrees. "Physician" was listed as the second career choice by 30% of the white students and 17% of the black students. The two groups differed in some of the motivation factors stated for considering any career choice and in their perceptions of the values that are offered in a career as a physician.

Factors used by program directors to select residents.

A national, stratified random sample of 405 graduate medical education program directors was surveyed on the way they selected their residents. The results from the 237 respondents reaffirm earlier studies which found that the interview was the most important selection variable. The results indicate that the recent increase in competition for residency positions has increased the importance of academic variables. For example, 86 percent of the respondents stated that they would not rank a candidate who had not passed the National Board of Medical Examiners Part I examination. Because 86 percent also stated that they give preference in ranking students to those who have done well in an elective at their hospitals, the senior year of medical school may be used as a "residency chase" rather than for the general professional education of the physician.

A caerulein-sensitive potentiation of the behavioral effects of apomorphine by dibutyryl-cAMP.

The dopaminergic behavioral effects of apomorphine in rats were evaluated using a rating scale. Caerulein, a decapeptide physiologically similar to cholecystokinin, enhanced at lower doses and inhibited at higher doses the behaviors induced by apomorphine. Dibutyryl-cAMP, but not dibutyryl-cGMP, potentiated apomorphine behaviors. This potentiation was inhibited by a high dose of caerulein. These data provide evidence for an opposing effect of cAMP and caerulein or cholecystokinin in modulating dopaminergic systems.

Report on a survey of program directors regarding selection factors in graduate medical education.

A national random sample of 25 percent of the graduate education program directors in internal medicine, family medicine, surgery, and pediatrics was sent a questionnaire; subjects were asked to judge the importance of 31 variables in the selection of house staff. A rank-ordering of variables for all respondents placed interpersonal skills demonstrated in the interview as number one. When rank order correlations were calculated for all possible pairs of program specializations, strong positive relationships were revealed. A two-way analysis of covariance was also undertaken to assess how selected program characteristics, such as size of program, type of program, and affiliation or nonaffiliation with a medical school, affected the judgment of the importance of the variables. The results have implications for further studies in several areas.